P2Y11, a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells

T. D. Nguyen, S. Meichle, U. S. Kim, T. Wong, M. W. Moody
2001 American Journal of Physiology - Gastrointestinal and Liver Physiology  
Nguyen, T. D., S. Meichle, U. S. Kim, T. Wong, and M. W. Moody. P2Y 11, a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells. Am J Physiol Gastrointest Liver Physiol 280: G795-G804, 2001.-Pancreatic duct epithelial cells (PDEC) mediate the exocrine secretion of fluid and electrolytes. We previously reported that ATP and UTP interact with P2Y 2 receptors on nontransformed canine PDEC to increase intracellular free Ca 2ϩ concentration ([Ca 2ϩ ]i) and
more » ... Ca 2ϩ ]i) and stimulate Ca 2ϩ -activated Cl Ϫ and K ϩ channels. We now report that ATP interacts with additional purinergic receptors to increase cAMP and activate Cl Ϫ channels. ATP, 2-methylthio-ATP, and ATP-␥-S stimulated a 4-to 10-fold cAMP increase with EC 50 of 10-100 M. Neither UTP nor adenosine stimulated a cAMP increase, excluding a role for P2Y2 or P1 receptors. Although UTP stimulated an 125 I Ϫ efflux that was fully inhibited by 1,2bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM), ATP stimulated a partially resistant efflux, suggesting activation of additional Cl Ϫ conductances through P2Y2-independent and Ca 2ϩ -independent pathways. In Ussing chambers, increased cAMP stimulated a much larger short-circuit current (Isc) increase from basolaterally permeabilized PDEC monolayers than increased [Ca 2ϩ ]i. Luminal ATP and UTP and serosal UTP stimulated a small Ca 2ϩ -type Isc increase, whereas serosal ATP stimulated a large cAMP-type I sc response. Serosal ATP effect was inhibited by P2 receptor blockers and unaffected by BAPTA-AM, supporting ATP activation of Cl Ϫ conductances through P2 receptors and a Ca 2ϩ -independent pathway. RT-PCR confirmed the presence of P2Y 11 receptor mRNA, the only P2Y receptor acting via cAMP. iodide efflux; adenosine 5Ј-triphosphate; Ussing chamber
doi:10.1152/ajpgi.2001.280.5.g795 pmid:11292586 fatcat:djhxpopjyzcxfguytm3vck4tdm