Role of endogenous cholecystokinin on vagally stimulated pancreatic secretion in dogs.

Pancreatic exocrine secretion was evoked by electrical stimulation of the vagus nerves (EVS) in dogs to determine whether a gut hormone was responsible for the pancreatic stimulatory activity. In 39 dogs, pancreatic juice was continuously collected to measure volume, bicarbonate, and amylase output, while portal and femoral venous plasma concentrations of gastrin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), and pancreatic polypeptide (PP) were determined by radioimmunoassay. EVS produced a significant increase in the pancreatic secretion. Although concentrations of all four peptides significantly increased in plasma, only CCK at the concentration in venous circulation was bioactive in dispersed rat pancreatic acini preparations. This bioactivity of CCK was completely blocked by CR 1409, a CCK-receptor antagonist. The pancreatic secretion by EVS was reduced significantly by intravenous MK-329 (formerly L364,718) to as low as 22% of control values and was completely suppressed by intravenous atropine. The increment in plasma CCK by EVS was also significantly suppressed by atropine. The present study indicates that increased pancreatic secretion by EVS is in part mediated by endogenous CCK.