PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE STIMULATES AMYLASE RELEASE AND CYCLIC ADENOSINE-MONOPHOSPHATE PRODUCTION IN PANCREATIC ACINAR-CELLS

Background. Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide member of the secretin/glucagon family of peptides, whi ch also includes vasoactive intestinal peptide (VIP). This study was d escribed to examine the effects of PACA-38 on pancreatic exocrine func tion in vitro. Methods. Amylase release and signal transduction pathwa ys were examined by using dispersed guinea pig acinar cells. Results. PACAP-38 produced dose-dependent increases in amylase release. Coincub ation of PACAP-38 (1 nmol/L) additively augmented amylase release stim ulated by cholecystokinin, carbachol, or bombesin. Coexposure with PAC AP-38 did not affect amylase release in response to maximally stimulat ory concentrations of VIP (1 nmol/L). The VIP antagonist, [N-Ac-Tyr(1) ,D-Phe(2)]-GRF(1-29)-NH2, abolished amylase release in response to eit her PACAP-38 or VIP. Dose-dependent increases in cyclic adenosine mono phosphate production were noted on exposure to PACAP-38, with a 70-fol d increment relative to the control value at 1 nmol/L PACAP-38. Inosit ol phosphate turnover and intracellular Ca2+ levels were not affected by PACAP-38 exposure. Conclusions. 1,2 guinea pig pancreatic acini, VI P-preferring receptors for PACAP-38 are functionally linked to adenyla te cyclase.