Characteristics of inhibition of pancreatic secretion by isoproterenol

The effect of isoproterenol on pancreatic secretion stimulated by the octapeptide of cholecystokinin (OP-CCK) was studied in dogs with gastric and pancreatic fistulas. Special precautions were taken to prevent entry of gastric acid into the duodenum and reflux of duodenal content into the stomach. OP-CCK increased volume and the outputs of bicarbonate and protein from the pancreas. Isoproterenol inhibited these pancreatic responses to OP-CCK, and the degree of inhibition was dose related. Propranolol blocked the inhibitory action of isoproterenol completely. Analysis of data by Michaelis-Menten kinetics revealed that there was competitive inhibition of protein output with noncompetitive inhibition of bicarbonate output. The experiments show that isoproterenol inhibits OP-CCK--stimulated pancreatic secretion by a beta-adrenergic mechanism. The kinetic analysis suggests that the intimate mechanisms involved in inhibition of protein and bicarbonate output by isoproterenol are different.