In a lab test using guinea‑pig pancreas cells, the brain‑derived peptide PACAP‑38 was found to make the cells release more digestive enzyme (amylase) by turning on a signaling molecule called cAMP. It worked together with other natural stimulators of the pancreas, but didn’t change calcium signals inside the cells.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide member of the secretin/glucagon family of peptides, which also includes vasoactive intestinal peptide (VIP). This study was designed to examine the effects of PACAP-38 on pancreatic exocrine function in vitro. Amylase release and signal transduction pathways were examined by using dispersed guinea pig acinar cells. PACAP-38 produced dose-dependent increases in amylase release. Coincubation of PACAP-38 (1 nmol/L) additively augmented amylase release stimulated by cholecystokinin, carbachol, or bombesin. Coexposure with PACAP-38 did not affect amylase release in response to maximally stimulatory concentrations of VIP (1 nmol/L). The VIP antagonist, [N-Ac-Tyr1,D-Phe2]-GRF(1-29)-NH2, abolished amylase release in response to either PACAP-38 or VIP. Dose-dependent increases in cyclic adenosine monophosphate production were noted on exposure to PACAP-38, with a 70-fold increment relative to the control value at 1 nmol/L PACAP-38. Inositol phosphate turnover and intracellular Ca2+ levels were not affected by PACAP-38 exposure. In guinea pig pancreatic acini, VIP preferring receptors for PACAP-38 are functionally linked to adenylate cyclase.