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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/R478    most recent 00163.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Song, Z. Articles by Stevens, W. PubMed PubMed Citation Articles by Song, Z. Articles by Stevens, W.

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

Department of Physiology and Biophysics, University of Colorado Denver School of Medicine, Denver, Colorado

Submitted 18 March 2009 ; accepted in final form 6 June 2009

Pharmacological studies demonstrated that ATP elevates intracellular calcium ([Ca²⁺]_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 [Ca²⁺]_i from both intracellular stores and Ca²⁺ 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 (80%) reduced the increase in [Ca²⁺]_i induced by the P2Y1R-specific agonist, 2-methylthio-ADP (2-MeSADP). In contrast, the increase in [Ca²⁺]_i was slightly (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 Ca²⁺ influx suggests that P2Y1Rs may regulate VP release by modifying ion channels such as stretch-inactivated cation channels.

ATP; hypothalamus; neurohypophyseal; supraoptic nucleus

This article has been cited by other articles:

				D. A. Gomes, Z. Song, W. Stevens, and C. D. Sladek Sustained stimulation of vasopressin and oxytocin release by ATP and phenylephrine requires recruitment of desensitization-resistant P2X purinergic receptors Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R940 - R949. [Abstract] [Full Text] [PDF]