Cyclic AMP and bicarbonate responses of the dog pancreas to vasoactive intestinal peptide (VIP) and secretion.

The effects of secretin (3 CU per kilogram) and vasoactive intestinal peptide (VIP; 8 mug per kilogram) on bicarbonate and cyclic AMP secretions in pancreatic juice (with pancreatic duct perfusion) and on pancreatic tissue cyclic AMP were investigated as a function of time in 13 anesthetized dogs. The peptides were given by rapid intravenous injection. Even 30 sec. after peptide administration, tissue cyclic AMP levels were elevated, reaching peak values within the first minute and a second peak at about 3 min. Bicarbonate and cyclic AMP secretions in pancreatic juice started with a lag of 1 min. after peptide injection. Following the injection of VIP, peak pancreatic response developed within the first 5 min. and the pancreatic response actually disappeared after 15 min., whereas secretion evoked by secretin was sustained for at least 30 min. The mean +/- S.D. observed maximal bicarbonate response to VIP (100 +/- 49 muEq./5 min.) was about one sixth of the maximum output following secretin (592 +/- 181 muEq./5 min.). Increases in pancreatic tissue and juice cyclic AMP caused by VIP were significant (p less than 0.05) at 1 and 4 min.; however, they were but moderate if compared with the rise achieved by secretin. The results presented confirm previous reports that VIP is a secretin-like partial agonist of pancreatic bicarbonate secretion and are compatible with the hypothesis that both secretin and VIP elicit canine pancreatic bicarbonate secretion via the second messenger system of cyclic AMP.