PMID- 19515986 OWN - NLM STAT- MEDLINE DCOM- 20090818 LR - 20200930 IS - 1522-1490 (Electronic) IS - 0363-6119 (Linking) VI - 297 IP - 2 DP - 2009 Aug TI - Role of purinergic P2Y1 receptors in regulation of vasopressin and oxytocin secretion. PG - R478-84 LID - 10.1152/ajpregu.00163.2009 [doi] AB - Pharmacological studies demonstrated that ATP elevates intracellular calcium ([Ca(2+)](i)) in supraoptic nucleus (SON) neurons primarily by activation of P2X2 and P2Y1 purinergic receptors [P2Y1R]. The current studies provide evidence for the presence of P2Y1R protein in SON neurons, evidence that activation of these P2Y1Rs induces an increase in [Ca(2+)](i) from both intracellular stores and Ca(2+) influx, and functional evidence that activation of P2Y1Rs induces vasopressin (VP) and oxytocin (OT) hormone release. Pretreatment of Fura-2 AM-loaded explants of the hypothalamo-neurohypophyseal system (HNS) with thapsigargin (TG) significantly (approximately 80%) reduced the increase in [Ca(2+)](i) induced by the P2Y1R-specific agonist, 2-methylthio-ADP (2-MeSADP). In contrast, the increase in [Ca(2+)](i) was slightly (approximately 20%) decreased in calcium-free medium. The calcium response to 2-MeSADP was completely blocked by the P2Y1R-specific antagonist, MRS2179 or by a combination of TG pretreatment and calcium-free medium. It was absent in P2Y1R knockout mice (P2Y1R(-/-)). 2-MeSADP significantly increased VP and OT release from perifused rat and wild-type mouse HNS explants compared with control. MRS2179 prevented this response in wild-type mouse, but it did not prevent ATP-induced hormone release from rat explants. 2-MeSADP did not induce hormone release from P2Y1R(-/-) explants. These findings support a potential role for P2Y1Rs in regulation of VP and OT release. The finding that P2Y1R activation induces a small Ca(2+) influx suggests that P2Y1Rs may regulate VP release by modifying ion channels such as stretch-inactivated cation channels. FAU - Song, Zhilin AU - Song Z AD - Dept. of Physiology and Biophysics, School of Medicine, Univ. of Colorado Denver, Denver, CO, USA. zhilin.song@ucdenver.edu FAU - Gomes, Dayane A AU - Gomes DA FAU - Stevens, Wanida AU - Stevens W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090610 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate) RN - 0 (P2ry1 protein, mouse) RN - 0 (P2ry1 protein, rat) RN - 0 (Purinergic P2 Receptor Agonists) RN - 0 (Purinergic P2 Receptor Antagonists) RN - 0 (Receptors, Purinergic P2) RN - 0 (Receptors, Purinergic P2Y1) RN - 0 (Thionucleotides) RN - 11000-17-2 (Vasopressins) RN - 34983-48-7 (methylthio-ADP) RN - 50-56-6 (Oxytocin) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 67526-95-8 (Thapsigargin) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Diphosphate/analogs & derivatives/pharmacology MH - Adenosine Triphosphate/pharmacology MH - Animals MH - Calcium Signaling/drug effects MH - Hypothalamo-Hypophyseal System/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neurons/metabolism MH - Oxytocin/*metabolism MH - Paraventricular Hypothalamic Nucleus/metabolism MH - Perfusion MH - Purinergic P2 Receptor Agonists MH - Purinergic P2 Receptor Antagonists MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Purinergic P2/*physiology MH - Receptors, Purinergic P2Y1 MH - Supraoptic Nucleus/*metabolism MH - Thapsigargin/pharmacology MH - Thionucleotides/pharmacology MH - Vasopressins/*metabolism EDAT- 2009/06/12 09:00 MHDA- 2009/08/19 09:00 CRDT- 2009/06/12 09:00 PHST- 2009/06/12 09:00 [entrez] PHST- 2009/06/12 09:00 [pubmed] PHST- 2009/08/19 09:00 [medline] AID - 00163.2009 [pii] AID - 10.1152/ajpregu.00163.2009 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R478-84. doi: 10.1152/ajpregu.00163.2009. Epub 2009 Jun 10.