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. PACAP127 and a PACAP receptor (PAC1) blocker, PACAP627, were locally administered to the pancreas. PACAP127 (0.0055 μg) increased basal insulin and glucagon secretion in a dose-dependent manner. PACAP627 (200 μg) blocked the glucagon response to PACAP127 (0.5 μg) by about 80%, while the insulin response remained unchanged. With a higher dose of PACAP627 (500 μg), both responses to PACAP127 were inhibited by more than 80%. In the presence of atropine with an equivalent dose (128.2 μg) of PACAP627 (500 μg) on a molar basis, the insulin response to PACAP127 was diminished by about 20%, while the glucagon response was enhanced by about 80%. The PACAP127-induced increase in pancreatic venous blood flow was blocked by PACAP627 but not by atropine. The study suggests that the endocrine secretagogue effect of PACAP127 is primarily mediated by the PAC1 receptor, and that PACAP127 may interact with muscarinic receptor function in PACAP-induced insulin and glucagon secretion in the canine pancreas in vivo.Key words: atropine, PACAP, PAC1, muscarinic, interaction.
The Difference δ-Cells Make in Glucose Control
