Regulation of Cyclic AMP Levels in Guinea Pig Pancreatic Ducts and Cultured Duct Epithelial Monolayers

Abstract

Pancreatic duct bicarbonate secretion is mediated primarily by secretin-induced elevation of intracellular cyclic AMP, although little is known of the effects of other physiological regulators on pancreatic duct cyclic AMP metabolism. We investigated the effects of secretin and several other potential agonists on cyclic AMP levels in isolated guinea pig main and interlobular pancreatic duct segments and in cultured duct epithelial monolayers. Secretin (0.1 microM) caused a five- to eightfold elevation of cyclic AMP in both isolated ducts and cultured monolayers (EC50 = 0.15 nM). Main duct segments, while responsive, were less so than segments of interlobular duct. In isolated duct segments, carbachol, bombesin, cholecystokinin, substance P, calcitonin gene-related peptide, glucagon, insulin, isoproterenol, neurotensin, and prostaglandin E2 did not significantly alter resting or secretin-stimulated cyclic AMP levels. In contrast, 0.1 microM vasoactive intestinal peptide significantly increased cyclic AMP to a level comparable to that evoked by an equal concentration of secretin. Somatostatin significantly attenuated the effects of a submaximal (physiological) dose of secretin on duct cyclic AMP levels without altering resting cyclic AMP levels, suggesting that somatostatin's effects on pancreatic duct fluid secretion are mediated by inhibition of adenylyl cyclase activity.