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, which also includes vasoactive intestinal peptide (VIP). This study was designed to examine the effects of PACAP-38 on pancreatic exocrine function in vitro.


METHODS
Amylase release and signal transduction pathways were examined by using dispersed guinea pig acinar cells.


RESULTS
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.


CONCLUSIONS
In guinea pig pancreatic acini, VIP preferring receptors for PACAP-38 are functionally linked to adenylate cyclase.
Kimball
B C
BC
Mulholland
M W
MW
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000032:analysis
D007295:Inositol Phosphates; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D000242:Cyclic AMP; D000681:Amylases; D002118:Calcium