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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2009-08, Vol.297 (2), p.R478-R484
• Main Authors: Song, Zhilin, Gomes, Dayane A, Stevens, Wanida
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - analogs & derivatives; Adenosine Diphosphate - pharmacology; Adenosine triphosphatase; Adenosine Triphosphate - pharmacology; Animals; Calcium; Calcium Signaling - drug effects; Hormones; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - secretion; Ions; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Neurons - metabolism; Oxytocin - secretion; Paraventricular Hypothalamic Nucleus - metabolism; Perfusion; Proteins; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2 - physiology; Receptors, Purinergic P2Y1; Rodents; Supraoptic Nucleus - metabolism; Thapsigargin - pharmacology; Thionucleotides - pharmacology; Vasopressins - secretion
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00163.2009

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 ([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 ( 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 ( 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. ATP; hypothalamus; neurohypophyseal; supraoptic nucleus Address for reprint requests and other correspondence: Z. Song, Dept. of Physiology and Biophysics, School of Medicine, Univ. of Colorado Denver, 12800 E. 19th Ave, MS 8307, P.O. Box 6511, Aurora, CO 80045. (e-mail: zhilin.song{at}ucdenver.edu )