{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:19:57Z","timestamp":1791145197200,"version":"4.1.0"},"reference-count":28,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2001,5,1]]},"abstract":"<jats:p>Pancreatic duct epithelial cells (PDEC) mediate the exocrine secretion of fluid and electrolytes. We previously reported that ATP and UTP interact with P2Y<jats:sub>2<\/jats:sub>receptors on nontransformed canine PDEC to increase intracellular free Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and stimulate Ca<jats:sup>2+<\/jats:sup>-activated Cl<jats:sup>\u2212<\/jats:sup>and K<jats:sup>+<\/jats:sup>channels. We now report that ATP interacts with additional purinergic receptors to increase cAMP and activate Cl<jats:sup>\u2212<\/jats:sup>channels. ATP, 2-methylthio-ATP, and ATP-\u03b3-S stimulated a 4- to 10-fold cAMP increase with EC<jats:sub>50<\/jats:sub>of 10\u2013100 \u03bcM. Neither UTP nor adenosine stimulated a cAMP increase, excluding a role for P2Y<jats:sub>2<\/jats:sub>or P1 receptors. Although UTP stimulated an<jats:sup>125<\/jats:sup>I<jats:sup>\u2212<\/jats:sup>efflux that was fully inhibited by 1,2-bis(2-aminophenoxy)ethane- N,N,N\u2032,N\u2032-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM), ATP stimulated a partially resistant efflux, suggesting activation of additional Cl<jats:sup>\u2212<\/jats:sup>conductances through P2Y<jats:sub>2<\/jats:sub>-independent and Ca<jats:sup>2+<\/jats:sup>-independent pathways. In Ussing chambers, increased cAMP stimulated a much larger short-circuit current ( I<jats:sub>sc<\/jats:sub>) increase from basolaterally permeabilized PDEC monolayers than increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Luminal ATP and UTP and serosal UTP stimulated a small Ca<jats:sup>2+<\/jats:sup>-type I<jats:sub>sc<\/jats:sub>increase, whereas serosal ATP stimulated a large cAMP-type I<jats:sub>sc<\/jats:sub>response. Serosal ATP effect was inhibited by P2 receptor blockers and unaffected by BAPTA-AM, supporting ATP activation of Cl<jats:sup>\u2212<\/jats:sup>conductances through P2 receptors and a Ca<jats:sup>2+<\/jats:sup>-independent pathway. RT-PCR confirmed the presence of P2Y<jats:sub>11<\/jats:sub>receptor mRNA, the only P2Y receptor acting via cAMP.<\/jats:p>","DOI":"10.1152\/ajpgi.2001.280.5.g795","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T15:41:20Z","timestamp":1514130080000},"page":"G795-G804","source":"Crossref","is-referenced-by-count":47,"title":["P2Y<sub>11<\/sub>, a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells"],"prefix":"10.1152","volume":"280","author":[{"given":"T. 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