CIDeRplusGeneral Information:
| Id: | 9,120 |
| Diseases: |
Arterial calcification, generalized, of infancy, 1
- [OMIM]
|
| Mammalia | |
| review | |
| Reference: | Bjelobaba I et al.(2015) Purinergic signaling pathways in endocrine system Auton Neurosci 191: 102-116 [PMID: 25960051] |
Interaction Information:
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 95656 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96827 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96828 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96829 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96830 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96831 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and several spliced forms of these subunits have been cloned. Each subunit is proposed to contain cytoplasmically located N-and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. Functional channels are organized as trimeric homomers and heteromers. P2XR subtypes differ with respect to their ligand selectivity profile, antagonist sensitivity, and cation selectivity. P2XR activation leads to inward currents associated with increased intracellular calcium and C-termini with consensus binding motifs for protein kinases, two transmembrane helices connected by a large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. |
|
Formal Description Interaction-ID: 96832 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96833 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96834 |
|
| Drugbank entries | Show/Hide entries for P2RY2 |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96835 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96836 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96837 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96838 |
|
| Drugbank entries | Show/Hide entries for P2RY12 |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96839 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96840 |
|
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96841 |
|
| Drugbank entries | Show/Hide entries for PLC |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96842 |
|
| Drugbank entries | Show/Hide entries for P2RY2 or PLC |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96843 |
|
| Drugbank entries | Show/Hide entries for PLC |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96844 |
|
| Drugbank entries | Show/Hide entries for PLC |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96845 |
|
| Drugbank entries | Show/Hide entries for PLC |
| Comment | ATP can be released from virtually every cell, in physiological and pathological conditions, and its extracellular concentrations can rise significantly. Some of the magnocellular, parvocellular, and autonomous nervous system neurons co-secrete ATP; endocrine and/or surrounding cells may release it too. The released ATP acts as an extracellular ligand for two families of purinergic receptors, two-transmembrane domain P2X receptor channels (P2XRs) and seven-transmembrane domain P2Y receptors (P2YRs), both being expressed in a variety of endocrine cells. Eight mammalian P2YRs have been identified and denoted P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R, and P2Y14R. Phylogenetically, these receptors form two subgroups. Members of the first group (1, 2, 4, and 6) signal through Gq/11 pathways, activating phospholipase C to generate inositol 1,4,5-trisphosphate and diacylglycerol. In excitable cells, inositol trisphosphate-induced calcium mobilization is frequently accompanied by calcium influx through Cav channels. Activation of MAP kinase and phospholipase D signaling pathways, both secondary to the activation of protein kinase C, has also been reported for P2YRs. The second group (11, 12, 13, and 14) shows variations in coupling to G proteins, including G i/o, Gs, and G16. |
|
Formal Description Interaction-ID: 96846 |
|
| Drugbank entries | Show/Hide entries for PLC |
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96847 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96848 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96849 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96850 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96851 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96852 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96853 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96854 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96855 |
|
| Drugbank entries | Show/Hide entries for ENPP1 |
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96856 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96857 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96858 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96859 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96860 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96861 |
|
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96862 |
|
| Drugbank entries | Show/Hide entries for NT5E |
| Comment | The duration and extent of ATP actions are limited by several ectonucleotidases, which hydrolyze purine nucleotides and nucleosides. Ectonucleotidase enzymes are present in endocrine cells. These enzymes include members of the ectonucleotide triphosphate diphosphohydrolase family (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPPase) and ecto-5'-nucleotidase (E-5NT), among others. E-NTPDases not only hydrolyze extracellular ATP and/or adenosine-5'-diphosphate (ADP) to adenosine 5'-monophosphate (AMP), but also metabolize other nucleotide tri- and diphosphates, including uridine triphosphate and uridine diphopshate, whereas E-NPPases hydrolyze ATP directly to AMP. AMP is hydrolyzed by E-5NT to adenosine. ADP and adenosine act as extracellular ligands too, ADP being a potent agonist for some P2YRs and adenosine an agonist for adenosine receptors (ARs). |
|
Formal Description Interaction-ID: 96863 |
|
| Drugbank entries | Show/Hide entries for NT5E or Adenosine |
| Comment | Four different adenosine-activated receptors have been cloned, termed A1R, A2AR, A2BR, and A3R. These receptors signal mainly through adenylyl cyclase. A1R and A3R are negatively coupled to adenylyl cyclase through pertussis toxin-sensitive Gi/o, whereas A2AR and A2BR are positively coupled through cholera toxin-sensitive Gs. The human A2BR has also been reported to signal through Gq/11-dependent phospholipase C. The intracellular pathways triggered by these receptors include Ca(v) channels and inwardly rectifying K+ channels, and activation of proteins involved in MAP kinase signaling. |
|
Formal Description Interaction-ID: 96864 |
|
| Drugbank entries | Show/Hide entries for Adenosine or ADORA1 |
| Comment | Four different adenosine-activated receptors have been cloned, termed A1R, A2AR, A2BR, and A3R. These receptors signal mainly through adenylyl cyclase. A1R and A3R are negatively coupled to adenylyl cyclase through pertussis toxin-sensitive Gi/o, whereas A2AR and A2BR are positively coupled through cholera toxin-sensitive Gs. The human A2BR has also been reported to signal through Gq/11-dependent phospholipase C. The intracellular pathways triggered by these receptors include Ca(v) channels and inwardly rectifying K+ channels, and activation of proteins involved in MAP kinase signaling. |
|
Formal Description Interaction-ID: 96865 |
|
| Drugbank entries | Show/Hide entries for Adenosine or ADORA2A |
| Comment | Four different adenosine-activated receptors have been cloned, termed A1R, A2AR, A2BR, and A3R. These receptors signal mainly through adenylyl cyclase. A1R and A3R are negatively coupled to adenylyl cyclase through pertussis toxin-sensitive Gi/o, whereas A2AR and A2BR are positively coupled through cholera toxin-sensitive Gs. The human A2BR has also been reported to signal through Gq/11-dependent phospholipase C. The intracellular pathways triggered by these receptors include Ca(v) channels and inwardly rectifying K+ channels, and activation of proteins involved in MAP kinase signaling. |
|
Formal Description Interaction-ID: 96866 |
|
| Drugbank entries | Show/Hide entries for Adenosine or ADORA2B |
| Comment | Four different adenosine-activated receptors have been cloned, termed A1R, A2AR, A2BR, and A3R. These receptors signal mainly through adenylyl cyclase. A1R and A3R are negatively coupled to adenylyl cyclase through pertussis toxin-sensitive Gi/o, whereas A2AR and A2BR are positively coupled through cholera toxin-sensitive Gs. The human A2BR has also been reported to signal through Gq/11-dependent phospholipase C. The intracellular pathways triggered by these receptors include Ca(v) channels and inwardly rectifying K+ channels, and activation of proteins involved in MAP kinase signaling. |
|
Formal Description Interaction-ID: 96867 |
|
| Drugbank entries | Show/Hide entries for Adenosine or ADORA3 |
| Comment | Magnocellular neurons are located within paraventricular nucleus (PVN) and supraoptic nucleus (SON) and project non-myelinated axons directly to the posterior pituitary (PP) or neurohypophysis, where the content of their secretory vesicles is released near fenestrated capillaries. The cell bodies of magnocellular PVN neurons, adjacent to the third ventricle, synthesize either vasopressin (VP) or oxytocin (OT), hormones which play important roles in water balance, blood pressure, parturition and lactation. Dynamics of VP and OT release from PP depends on the rate and pattern of neuronal electrical activity, which is neuron type-specific. |
|
Formal Description Interaction-ID: 96868 |
|
| Comment | Magnocellular neurons are located within paraventricular nucleus (PVN) and supraoptic nucleus (SON) and project non-myelinated axons directly to the posterior pituitary (PP) or neurohypophysis, where the content of their secretory vesicles is released near fenestrated capillaries. The cell bodies of magnocellular PVN neurons, adjacent to the third ventricle, synthesize either vasopressin (VP) or oxytocin (OT), hormones which play important roles in water balance, blood pressure, parturition and lactation. Dynamics of VP and OT release from PP depends on the rate and pattern of neuronal electrical activity, which is neuron type-specific. |
|
Formal Description Interaction-ID: 96869 |
|
| Drugbank entries | Show/Hide entries for |
| Comment | Several lines of evidence indicate that the purinergic signaling pathway is operative in the magnocellular neurosecretory system and posterior pituitary (PP) and plays important role(s) in controlling neuronal activity. |
|
Formal Description Interaction-ID: 96870 |
affects_activity of tissue/cell line |
| Comment | Purinergic signaling in supraoptic nucleus (SON) and paraventricular nucleus (PVN) is not limited to the neurons and their nerve endings in the posterior pituitary (PP), but also includes astrocytes in these nuclei and pituicytes in PP. It was shown that glial cells contribute to ATP release in the PVN. Astrocytes in SON express calcium mobilizing P2Y1R as well as calcium-controlled small K+ channels. P2Y1R activation may account for stimulation of these channels and synchronization of electrical activity with calcium mobilization. The majority of pituicytes in primary cultures respond to ATP with a rapid phospholipase C-dependent and extracellular calcium-independent rise in Ca2+i indicating the presence of functional P2YRs in these cells. |
|
Formal Description Interaction-ID: 96884 |
|
| Comment | Purinergic signaling in supraoptic nucleus (SON) and paraventricular nucleus (PVN) is not limited to the neurons and their nerve endings in the posterior pituitary (PP), but also includes astrocytes in these nuclei and pituicytes in PP. It was shown that glial cells contribute to ATP release in the PVN. Astrocytes in SON express calcium mobilizing P2Y1R as well as calcium-controlled small K+ channels. P2Y1R activation may account for stimulation of these channels and synchronization of electrical activity with calcium mobilization. The majority of pituicytes in primary cultures respond to ATP with a rapid phospholipase C-dependent and extracellular calcium-independent rise in Ca2+i indicating the presence of functional P2YRs in these cells. |
|
Formal Description Interaction-ID: 96886 |
|
| Comment | Purinergic signaling in supraoptic nucleus (SON) and paraventricular nucleus (PVN) is not limited to the neurons and their nerve endings in the posterior pituitary (PP), but also includes astrocytes in these nuclei and pituicytes in PP. It was shown that glial cells contribute to ATP release in the PVN. Astrocytes in SON express calcium mobilizing P2Y1R as well as calcium-controlled small K+ channels. P2Y1R activation may account for stimulation of these channels and synchronization of electrical activity with calcium mobilization. The majority of pituicytes in primary cultures respond to ATP with a rapid phospholipase C-dependent and extracellular calcium-independent rise in Ca2+i indicating the presence of functional P2YRs in these cells. |
|
Formal Description Interaction-ID: 96887 |
tissue/cell line increases_quantity of drug/chemical compound |
| Comment | Purinergic signaling in supraoptic nucleus (SON) and paraventricular nucleus (PVN) is not limited to the neurons and their nerve endings in the posterior pituitary (PP), but also includes astrocytes in these nuclei and pituicytes in PP. It was shown that glial cells contribute to ATP release in the PVN. Astrocytes in SON express calcium mobilizing P2Y1R as well as calcium-controlled small K+ channels. P2Y1R activation may account for stimulation of these channels and synchronization of electrical activity with calcium mobilization. The majority of pituicytes in primary cultures respond to ATP with a rapid phospholipase C-dependent and extracellular calcium-independent rise in Ca2+i indicating the presence of functional P2YRs in these cells. |
|
Formal Description Interaction-ID: 96888 |
|
| Comment | Purinergic signaling in supraoptic nucleus (SON) and paraventricular nucleus (PVN) is not limited to the neurons and their nerve endings in the posterior pituitary (PP), but also includes astrocytes in these nuclei and pituicytes in PP. It was shown that glial cells contribute to ATP release in the PVN. Astrocytes in SON express calcium mobilizing P2Y1R as well as calcium-controlled small K+ channels. P2Y1R activation may account for stimulation of these channels and synchronization of electrical activity with calcium mobilization. The majority of pituicytes in primary cultures respond to ATP with a rapid phospholipase C-dependent and extracellular calcium-independent rise in Ca2+i indicating the presence of functional P2YRs in these cells. |
|
Formal Description Interaction-ID: 96889 |
|
| Comment | Supraoptic nucleus (SON) neurons express functional presynaptic and extrasynaptic P2X2R and P2X4R that modulate glutamate and GABA release and control the electrical excitability. |
|
Formal Description Interaction-ID: 96890 |
|
| Comment | Supraoptic nucleus (SON) neurons express functional presynaptic and extrasynaptic P2X2R and P2X4R that modulate glutamate and GABA release and control the electrical excitability. |
|
Formal Description Interaction-ID: 96891 |
|
| Comment | Supraoptic nucleus (SON) neurons express functional presynaptic and extrasynaptic P2X2R and P2X4R that modulate glutamate and GABA release and control the electrical excitability. |
|
Formal Description Interaction-ID: 96892 |
|
| Comment | Supraoptic nucleus (SON) neurons express functional presynaptic and extrasynaptic P2X2R and P2X4R that modulate glutamate and GABA release and control the electrical excitability. |
|
Formal Description Interaction-ID: 96893 |
|
| Comment | In the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, there is a circadian rhythm in ATP intracellular levels and release, the latter suggesting that these oscillations represent a physiological output of the mammalian cellular clock. In addition, ATP release in SCN astrocytes is coupled with mitochondrial calcium signaling. Once in the extracellular space, ATP might activate P2X2R, P2X4R, P2X6R, and/or P2XR7, since these mRNA transcripts were found in rat SCN. P2X5R protein expression was also confirmed in SCN and its ability to form heterotrimers with P2X2 subunits may be of some functional importance in the nervous tissue. Activation of presynaptic P2X2R potentiates inhibitory synaptic transmission within the SCN. |
|
Formal Description Interaction-ID: 96894 |
|
| Comment | The medial preoptic area and arcuate nucleus contain gonadotropin-releasing hormone (GnRH) neurons projecting to the median eminence, where they release this decapeptid, which regulates hypothalamic-pituitary-gonadal axes in a sex-specific manner. The arcuate nucleus also contains neurons that control other endocrine functions of the anterior pituitary by secreting both releasing and inhibitory neurohormones at the median eminence, including growth hormone-releasing hormone (GHRH) and dopamine. GHRH regulates the hypothalamic-pituitary-growth hormone axis and dopamine regulates the hypothalamic-pituitary-prolactin axis. |
|
Formal Description Interaction-ID: 96895 |
|
| Comment | The medial preoptic area and arcuate nucleus contain gonadotropin-releasing hormone (GnRH) neurons projecting to the median eminence, where they release this decapeptid, which regulates hypothalamic-pituitary-gonadal axes in a sex-specific manner. The arcuate nucleus also contains neurons that control other endocrine functions of the anterior pituitary by secreting both releasing and inhibitory neurohormones at the median eminence, including growth hormone-releasing hormone (GHRH) and dopamine. GHRH regulates the hypothalamic-pituitary-growth hormone axis and dopamine regulates the hypothalamic-pituitary-prolactin axis. |
|
Formal Description Interaction-ID: 96896 |
|
| Comment | The medial preoptic area and arcuate nucleus contain gonadotropin-releasing hormone (GnRH) neurons projecting to the median eminence, where they release this decapeptid, which regulates hypothalamic-pituitary-gonadal axes in a sex-specific manner. The arcuate nucleus also contains neurons that control other endocrine functions of the anterior pituitary by secreting both releasing and inhibitory neurohormones at the median eminence, including growth hormone-releasing hormone (GHRH) and dopamine. GHRH regulates the hypothalamic-pituitary-growth hormone axis and dopamine regulates the hypothalamic-pituitary-prolactin axis. |
|
Formal Description Interaction-ID: 96897 |
|
| Drugbank entries | Show/Hide entries for Dopamine |
| Comment | The hypothalamic-pituitary-gonadal axis consists of three levels: the parvocellular hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the adenohypophysial gonadotrophs, and gonads (testes in the male and ovaries in the females). GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), together with sex steroids, including androgens and estrogens, are the hormonal products of this axis. GnRH is a 10-amino-acid hypothalamic neuropeptide that controls the function of reproductive axis. It is released by hypothalamic GnRH neurons in a pulsatile manner and reaches gonadotrophs through the portal blood, leading to stimulation of synthesis and release of LH and FSH, which in turn control the endocrine and gametogenesis functions of ovaries and testes. The feedback of gonadal steroid hormones at the level of hypothalamus and pituitary plays a major role in synchronized activity of hypothalamic-pituitary-gonadal axis. |
|
Formal Description Interaction-ID: 96899 |
|
| Comment | The hypothalamic-pituitary-gonadal axis consists of three levels: the parvocellular hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the adenohypophysial gonadotrophs, and gonads (testes in the male and ovaries in the females). GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), together with sex steroids, including androgens and estrogens, are the hormonal products of this axis. GnRH is a 10-amino-acid hypothalamic neuropeptide that controls the function of reproductive axis. It is released by hypothalamic GnRH neurons in a pulsatile manner and reaches gonadotrophs through the portal blood, leading to stimulation of synthesis and release of LH and FSH, which in turn control the endocrine and gametogenesis functions of ovaries and testes. The feedback of gonadal steroid hormones at the level of hypothalamus and pituitary plays a major role in synchronized activity of hypothalamic-pituitary-gonadal axis. |
|
Formal Description Interaction-ID: 96900 |
process HPG axis increases_quantity of complex/PPI Luteinizing hormone |
| Comment | The hypothalamic-pituitary-gonadal axis consists of three levels: the parvocellular hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the adenohypophysial gonadotrophs, and gonads (testes in the male and ovaries in the females). GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), together with sex steroids, including androgens and estrogens, are the hormonal products of this axis. GnRH is a 10-amino-acid hypothalamic neuropeptide that controls the function of reproductive axis. It is released by hypothalamic GnRH neurons in a pulsatile manner and reaches gonadotrophs through the portal blood, leading to stimulation of synthesis and release of LH and FSH, which in turn control the endocrine and gametogenesis functions of ovaries and testes. The feedback of gonadal steroid hormones at the level of hypothalamus and pituitary plays a major role in synchronized activity of hypothalamic-pituitary-gonadal axis. |
|
Formal Description Interaction-ID: 96901 |
process HPG axis increases_quantity of complex/PPI Follicle-stimulating hormone |
| Comment | The hypothalamic-pituitary-gonadal axis consists of three levels: the parvocellular hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the adenohypophysial gonadotrophs, and gonads (testes in the male and ovaries in the females). GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), together with sex steroids, including androgens and estrogens, are the hormonal products of this axis. GnRH is a 10-amino-acid hypothalamic neuropeptide that controls the function of reproductive axis. It is released by hypothalamic GnRH neurons in a pulsatile manner and reaches gonadotrophs through the portal blood, leading to stimulation of synthesis and release of LH and FSH, which in turn control the endocrine and gametogenesis functions of ovaries and testes. The feedback of gonadal steroid hormones at the level of hypothalamus and pituitary plays a major role in synchronized activity of hypothalamic-pituitary-gonadal axis. |
|
Formal Description Interaction-ID: 96902 |
process HPG axis increases_quantity of drug/chemical compound Estrogen |
| Comment | The hypothalamic-pituitary-gonadal axis consists of three levels: the parvocellular hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the adenohypophysial gonadotrophs, and gonads (testes in the male and ovaries in the females). GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), together with sex steroids, including androgens and estrogens, are the hormonal products of this axis. GnRH is a 10-amino-acid hypothalamic neuropeptide that controls the function of reproductive axis. It is released by hypothalamic GnRH neurons in a pulsatile manner and reaches gonadotrophs through the portal blood, leading to stimulation of synthesis and release of LH and FSH, which in turn control the endocrine and gametogenesis functions of ovaries and testes. The feedback of gonadal steroid hormones at the level of hypothalamus and pituitary plays a major role in synchronized activity of hypothalamic-pituitary-gonadal axis. |
|
Formal Description Interaction-ID: 96903 |
process HPG axis increases_quantity of drug/chemical compound Androgen |
| Comment | Adenosine amplifies FSH action in granulosa cells and LH action in luteal cells of rat and human ovaries. The amplifying role of adenosine on cAMP accumulation in granulosa cells was more robust in response to LH and the stimulatory action of adenosine is operative in both preovulatory and luteal granulosa cells and is mediated by A2Rs. |
|
Formal Description Interaction-ID: 96904 |
|
| Drugbank entries | Show/Hide entries for Adenosine |
| Comment | Adenosine amplifies FSH action in granulosa cells and LH action in luteal cells of rat and human ovaries. The amplifying role of adenosine on cAMP accumulation in granulosa cells was more robust in response to LH and the stimulatory action of adenosine is operative in both preovulatory and luteal granulosa cells and is mediated by A2Rs. |
|
Formal Description Interaction-ID: 96905 |
|
| Drugbank entries | Show/Hide entries for Adenosine |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96906 |
|
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96907 |
|
| Drugbank entries | Show/Hide entries for Adenosine |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96908 |
|
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96909 |
|
| Drugbank entries | Show/Hide entries for Adenosine |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96910 |
|
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96911 |
|
| Drugbank entries | Show/Hide entries for Adenosine |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96912 |
complex/PPI Follicle-stimulating hormone decreases_quantity of drug/chemical compound |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96913 |
complex/PPI Follicle-stimulating hormone decreases_quantity of drug/chemical compound |
| Comment | In addition to LH and FSH, ATP and adenosine act as modulators of testicular cells, including Sertoli cells, spermatogonia, and Leydig cells. The Sertoli cells release ATP endogenously. The basal compartment of the seminiferous epithelium and Leydig cells express pannexin channels, which could account for ATP release. In Sertoli cells from immature rats, ATP and ADP are hydrolyzed by E-NTPDase1, whereas E-5NT and ecto-adenosine deaminase (ADA) account for termination of purinergic signaling, hydrolyzing AMP and adenosine, respectively. Moreover, FSH stimulates ATP and ADP hydrolysis in Sertoli cells and therefore increases extracellular adenosine levels. A significant increase in ectonucleotidase activity in these cells was observed during sexual maturation, implying that purinergic signaling may be important for male reproduction. Interstitial macrophages in testis also express E-ENTPDase1, which could contribute to termination of the agonistic action of ATP. |
|
Formal Description Interaction-ID: 96914 |
complex/PPI Follicle-stimulating hormone increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | In Sertoli cells, ATP elevates cytosolic calcium and steroid secretion, probably by activating both sodium/calcium influx-dependent P2X4R and P2X7R and calcium mobilizing P2Y1R and P2Y2R. Extracellular ATP also increases the sperm fertilizing potential in vitro, presumably by activating sodium-conducting ATP-gated channels. P2X2R, P2X3R, and P2X5R subtypes have been identified in various germ cell types, whereas Sertoli cells express P2X2R, P2X3R, and P2X7R as well as the calcium-mobilizing P2Y2R. Calcium signals generated by activated P2XRs and P2YRs in mouse Sertoli cells are coupled to mobilization of mitochondrial calcium. In addition to P2XRs and P2YRs, A1Rs have been found in the crude particulate preparation from rat testis and Sertoli cell enriched cultures. Their activation leads to inhibition of the FSH-induced cAMP response in a pertussis toxin-sensitive manner. Spermatogenic cells also express cAMP-inhibiting A1Rs. |
|
Formal Description Interaction-ID: 96915 |
|
| Comment | In rat and mouse Leydig cells, ATP increases cytosolic calcium and testosterone secretion, the latter being dependent on sustained calcium influx by activated P2YRs, indicating its modulatory role in androgen production through activation of P2XRs. Functional P2X2Rs have also been identified in mouse Leydig cells using whole cell current measurements and specific agonist and antagonists. Western blot experiments revealed that in addition to P2X2R, mouse Leydig cells express P2X4R, P2X6R, and P2X7R and their functionality is confirmed by electrophysiological measurements of the whole-cell current. |
|
Formal Description Interaction-ID: 96916 |
|
| Comment | Parvocellular thyrotropin-releasing hormone (TRH)-secreting neurons, located predominantly in the paraventricular nucleus (PVN) of the hypothalamus, project their axon terminals to median eminence and release the tripeptide TRH into the hypophyseal portal system. The released TRH stimulates thyroid-stimulating hormone (TSH) synthesis and secretion in pituitary thyrotrophs. In the thyroid gland, TSH then stimulates the biosynthesis of the thyroid hormones, thyroxin (T4) and its modified product triiodothyronine (T3). TSH acts primarily via its receptors coupled to the adenylyl cyclase signaling pathway and cross-coupled to the phospholipase C signaling pathway. Thyroid hormones themselves have negative feedback control over the hypothalamus and anterior pituitary, thus controlling the release of both TRH and TSH. The proper function of this axis and its feedback mechanisms is responsible for normal development, differentiation, thermogenesis, and reproduction. |
|
Formal Description Interaction-ID: 96917 |
|
| Comment | Parvocellular thyrotropin-releasing hormone (TRH)-secreting neurons, located predominantly in the paraventricular nucleus (PVN) of the hypothalamus, project their axon terminals to median eminence and release the tripeptide TRH into the hypophyseal portal system. The released TRH stimulates thyroid-stimulating hormone (TSH) synthesis and secretion in pituitary thyrotrophs. In the thyroid gland, TSH then stimulates the biosynthesis of the thyroid hormones, thyroxin (T4) and its modified product triiodothyronine (T3). TSH acts primarily via its receptors coupled to the adenylyl cyclase signaling pathway and cross-coupled to the phospholipase C signaling pathway. Thyroid hormones themselves have negative feedback control over the hypothalamus and anterior pituitary, thus controlling the release of both TRH and TSH. The proper function of this axis and its feedback mechanisms is responsible for normal development, differentiation, thermogenesis, and reproduction. |
|
Formal Description Interaction-ID: 96918 |
|
| Comment | Parvocellular thyrotropin-releasing hormone (TRH)-secreting neurons, located predominantly in the paraventricular nucleus (PVN) of the hypothalamus, project their axon terminals to median eminence and release the tripeptide TRH into the hypophyseal portal system. The released TRH stimulates thyroid-stimulating hormone (TSH) synthesis and secretion in pituitary thyrotrophs. In the thyroid gland, TSH then stimulates the biosynthesis of the thyroid hormones, thyroxin (T4) and its modified product triiodothyronine (T3). TSH acts primarily via its receptors coupled to the adenylyl cyclase signaling pathway and cross-coupled to the phospholipase C signaling pathway. Thyroid hormones themselves have negative feedback control over the hypothalamus and anterior pituitary, thus controlling the release of both TRH and TSH. The proper function of this axis and its feedback mechanisms is responsible for normal development, differentiation, thermogenesis, and reproduction. |
|
Formal Description Interaction-ID: 96919 |
complex/PPI Thyroid-stimulating hormone increases_quantity of drug/chemical compound |
| Comment | Maintenance of homeostasis requires continuous adaptation to stressors. Adaptive responses include: i) activation of the autonomic nervous system, leading to increase in cardiovascular and respiratory activity; ii) activation of the hypothalamic‚Äďpituitary‚Äďadrenal (HPA) axis, leading to increased energy availability; iii) behavioral changes, leading to arousal, defense and escape reactions. The 41-amino acid hypothalamic peptide CRH is the main regulator of the HPA axis activity during stress by stimulating the secretion and synthesis of ACTH in pituitary corticotrophs. The released ACTH stimulates secretion of glucocorticoids and androgens, steroid hormones of the adrenal cortex. Glucocorticoid receptors are expressed in corticotrophs and CRH neurons and contribute to negative feedback actions of glucocorticoids on ACTH secretion. In addition, there are neuronal pathways linked to release of catecholamines from the adrenal medulla, in response to stress. |
|
Formal Description Interaction-ID: 96920 |
|
| Drugbank entries | Show/Hide entries for CRH |
| Comment | Maintenance of homeostasis requires continuous adaptation to stressors. Adaptive responses include: i) activation of the autonomic nervous system, leading to increase in cardiovascular and respiratory activity; ii) activation of the hypothalamic‚Äďpituitary‚Äďadrenal (HPA) axis, leading to increased energy availability; iii) behavioral changes, leading to arousal, defense and escape reactions. The 41-amino acid hypothalamic peptide CRH is the main regulator of the HPA axis activity during stress by stimulating the secretion and synthesis of ACTH in pituitary corticotrophs. The released ACTH stimulates secretion of glucocorticoids and androgens, steroid hormones of the adrenal cortex. Glucocorticoid receptors are expressed in corticotrophs and CRH neurons and contribute to negative feedback actions of glucocorticoids on ACTH secretion. In addition, there are neuronal pathways linked to release of catecholamines from the adrenal medulla, in response to stress. |
|
Formal Description Interaction-ID: 96921 |
|
| Drugbank entries | Show/Hide entries for CRH |
| Comment | Maintenance of homeostasis requires continuous adaptation to stressors. Adaptive responses include: i) activation of the autonomic nervous system, leading to increase in cardiovascular and respiratory activity; ii) activation of the hypothalamic‚Äďpituitary‚Äďadrenal (HPA) axis, leading to increased energy availability; iii) behavioral changes, leading to arousal, defense and escape reactions. The 41-amino acid hypothalamic peptide CRH is the main regulator of the HPA axis activity during stress by stimulating the secretion and synthesis of ACTH in pituitary corticotrophs. The released ACTH stimulates secretion of glucocorticoids and androgens, steroid hormones of the adrenal cortex. Glucocorticoid receptors are expressed in corticotrophs and CRH neurons and contribute to negative feedback actions of glucocorticoids on ACTH secretion. In addition, there are neuronal pathways linked to release of catecholamines from the adrenal medulla, in response to stress. |
|
Formal Description Interaction-ID: 96922 |
|
| Comment | Maintenance of homeostasis requires continuous adaptation to stressors. Adaptive responses include: i) activation of the autonomic nervous system, leading to increase in cardiovascular and respiratory activity; ii) activation of the hypothalamic‚Äďpituitary‚Äďadrenal (HPA) axis, leading to increased energy availability; iii) behavioral changes, leading to arousal, defense and escape reactions. The 41-amino acid hypothalamic peptide CRH is the main regulator of the HPA axis activity during stress by stimulating the secretion and synthesis of ACTH in pituitary corticotrophs. The released ACTH stimulates secretion of glucocorticoids and androgens, steroid hormones of the adrenal cortex. Glucocorticoid receptors are expressed in corticotrophs and CRH neurons and contribute to negative feedback actions of glucocorticoids on ACTH secretion. In addition, there are neuronal pathways linked to release of catecholamines from the adrenal medulla, in response to stress. |
|
Formal Description Interaction-ID: 96923 |
|
| Comment | Maintenance of homeostasis requires continuous adaptation to stressors. Adaptive responses include: i) activation of the autonomic nervous system, leading to increase in cardiovascular and respiratory activity; ii) activation of the hypothalamic‚Äďpituitary‚Äďadrenal (HPA) axis, leading to increased energy availability; iii) behavioral changes, leading to arousal, defense and escape reactions. The 41-amino acid hypothalamic peptide CRH is the main regulator of the HPA axis activity during stress by stimulating the secretion and synthesis of ACTH in pituitary corticotrophs. The released ACTH stimulates secretion of glucocorticoids and androgens, steroid hormones of the adrenal cortex. Glucocorticoid receptors are expressed in corticotrophs and CRH neurons and contribute to negative feedback actions of glucocorticoids on ACTH secretion. In addition, there are neuronal pathways linked to release of catecholamines from the adrenal medulla, in response to stress. |
|
Formal Description Interaction-ID: 96924 |
|
| Comment | Growth hormone (GH) secretion by pituitary somatotrophs is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by hypothalamic somatostatin. The released GH exerts a short-loop negative feedback through activation of somatostatin neurons that directly synapse with GHRH neurons. Negative feedback control of GH secretion also occurs at the pituitary level and is mediated by insulin-like growth factor type 1 and by free fatty acids. Ghrelin secreted from the stomach also contributes to the control of GH release at the hypothalamic and pituitary levels. |
|
Formal Description Interaction-ID: 96925 |
|
| Comment | Growth hormone (GH) secretion by pituitary somatotrophs is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by hypothalamic somatostatin. The released GH exerts a short-loop negative feedback through activation of somatostatin neurons that directly synapse with GHRH neurons. Negative feedback control of GH secretion also occurs at the pituitary level and is mediated by insulin-like growth factor type 1 and by free fatty acids. Ghrelin secreted from the stomach also contributes to the control of GH release at the hypothalamic and pituitary levels. |
|
Formal Description Interaction-ID: 96926 |
|
| Comment | Growth hormone (GH) secretion by pituitary somatotrophs is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by hypothalamic somatostatin. The released GH exerts a short-loop negative feedback through activation of somatostatin neurons that directly synapse with GHRH neurons. Negative feedback control of GH secretion also occurs at the pituitary level and is mediated by insulin-like growth factor type 1 and by free fatty acids. Ghrelin secreted from the stomach also contributes to the control of GH release at the hypothalamic and pituitary levels. |
|
Formal Description Interaction-ID: 96927 |
|
| Drugbank entries | Show/Hide entries for IGF1 |
| Comment | Growth hormone (GH) secretion by pituitary somatotrophs is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by hypothalamic somatostatin. The released GH exerts a short-loop negative feedback through activation of somatostatin neurons that directly synapse with GHRH neurons. Negative feedback control of GH secretion also occurs at the pituitary level and is mediated by insulin-like growth factor type 1 and by free fatty acids. Ghrelin secreted from the stomach also contributes to the control of GH release at the hypothalamic and pituitary levels. |
|
Formal Description Interaction-ID: 96928 |
|
| Comment | Growth hormone (GH) secretion by pituitary somatotrophs is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by hypothalamic somatostatin. The released GH exerts a short-loop negative feedback through activation of somatostatin neurons that directly synapse with GHRH neurons. Negative feedback control of GH secretion also occurs at the pituitary level and is mediated by insulin-like growth factor type 1 and by free fatty acids. Ghrelin secreted from the stomach also contributes to the control of GH release at the hypothalamic and pituitary levels. |
|
Formal Description Interaction-ID: 96929 |
|
| Comment | Purinergic signaling pathways are found in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. |
|
Formal Description Interaction-ID: 96930 |
|
| Comment | Purinergic signaling pathways are found in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. |
|
Formal Description Interaction-ID: 96932 |
|
| Comment | Purinergic signaling pathways are found in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. |
|
Formal Description Interaction-ID: 96933 |
|
| Comment | Purinergic signaling pathways are found in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. |
|
Formal Description Interaction-ID: 96934 |
|
| Comment | Purinergic signaling pathways are found in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. |
|
Formal Description Interaction-ID: 96935 |
|