Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells

Abstract

Extracellular triphosphate nucleotides, such as ATP, may regulate various cellular functions through specific cell surface receptors. We examine in this report the different secretory effects of ATP and analogs on nontransformed dog pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine 5'-O-(3-thiotriphosphate), and, to a lesser extent, β,γ-methylene-ATP, but not adenosine, stimulated 125I- efflux from PDEC, suggesting a primary role for P(2Y2) receptors, 2) ATP-stimulated 125I- efflux was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting mediation through Ca 2+- activated Cl - channels, 3) ATP stimulated an 86Rb + efflux sensitive to BaCl 2 and charybdotoxin, thus likely occurring through Ca 2+-activated K + channels, 4) serosal or luminal addition of UTP activated apical Cl - conductance and basolateral K + conductance when nystatin-permeabilized PDEC were studied in an Ussing chamber, suggesting the expression of P(2Y2) receptors on both sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases intracellular Ca 2+ concentration ([Ca 2+](i)). In conclusion, ATP and UTP interact with P(2Y2) receptors on nontransformed PDEC to increase [Ca 2+](i), stimulate mucin secretion, and activate ion conductances; these findings have implications for pancreatic exocrine function in both health and disease, such as cystic fibrosis.