REGULATION OF CYCLIC-AMP LEVELS IN GUINEA-PIG PANCREATIC DUCTS AND CULTURED DUCT EPITHELIAL MONOLAYERS

Pancreatic duct bicarbonate secretion is mediated primarily by secreti n-induced elevation of intracellular cyclic AMP, although little is kn own of the effects of other physiological regulators on pancreatic duc t cyclic AMP metabolism. We investigated the effects of secretin and s everal other potential agonists on cyclic AMP levels in isolated guine a pig main and interlobular pancreatic duct segments and in cultured d uct epithelial monolayers. Secretin (0.1 mu M) caused a five- to eight fold elevation of cyclic AMP in both isolated ducts and cultured monol ayers (EC(50) = 0.15 nM). Main duct segments, while responsive, were l ess so than segments of interlobular duct. In isolated duct segments, carbachol, bombesin, cholecystokinin, substance P, calcitonin gene-rel ated peptide, glucagon, insulin, isoproterenol, neurotensin, and prost aglandin E(2) did not significantly alter resting or secretin-stimulat ed cyclic AMP levels. In contrast, 0.1 mu M vasoactive intestinal pept ide significantly increased cyclic AMP to a level comparable to that e voked by an equal concentration of secretin. Somatostatin significantl y attenuated the effects of a submaximal (physiological) dose of secre tin on duct cyclic AMP levels without altering resting cyclic AMP leve ls, suggesting that somatostatin's effects on pancreatic duct fluid se cretion are mediated by inhibition of adenylyl cyclase activity.