Effects of PACAP(1-27) on the canine endocrine pancreas in vivo: interaction with cholinergic mechanism

The aim of the present study was to characterize the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the endocrine pancreas in anesthetized dogs. PACAP(1-27) and a PACAP receptor (PAC(1)) blocker, PACAP(6-27), were locally administered to the pancreas. PACAP(1-27) (0.005-5 microg) increased basal insulin and glucagon secretion in a dose-dependent manner. PACAP(6-27) (200 microg) blocked the glucagon response to PACAP(1-27) (0.5 microg) by about 80%, while the insulin response remained unchanged. With a higher dose of PACAP(6-27) (500 microg), both responses to PACAP(1-27) were inhibited by more than 80%. In the presence of atropine with an equivalent dose (128.2 microg) of PACAP(6-27) (500 microg) on a molar basis, the insulin response to PACAP(1-27) was diminished by about 20%, while the glucagon response was enhanced by about 80%. The PACAP(1-27)-induced increase in pancreatic venous blood flow was blocked by PACAP(6-27) but not by atropine. The study suggests that the endocrine secretagogue effect of PACAP(1-27) is primarily mediated by the PAC(1) receptor, and that PACAP(1-27) may interact with muscarinic receptor function in PACAP-induced insulin and glucagon secretion in the canine pancreas in vivo.