Role of purinergic P2Y1 receptors in regulation of vasopressin and oxytocin secretion

Song Z, Gomes DA, Stevens W. Role of purinergic P2Y1 receptors in regulation of vasopressin and oxytocin secretion. Am J Physiol Regul Integr Comp Physiol 297: R478-R484, 2009. First published June 10, 2009; doi:10.1152/ajpregu.00163.2009.-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; (18)]. 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 (similar to 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 (similar to 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.