Effects of peptide histidine isoleucine on pancreatic exocrine secretion in anaesthetized dogs

1. The effects of peptide histidine isoleucine (PHI) on pancreatic exocrine secretion were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of vasoactive intestinal peptide (VIP), secretin and glucagon. 2. Each peptide tested was injected intra-arterially (i.a.) as a single bolus. Graded doses of PHI (3-300 nmol/kg), VIP (1-100 nmol/kg) and secretin (0.01-0.3 nmol/kg) caused dose-dependent increases in the secretion of pancreatic juice and bicarbonate outputs, but had little effect on the protein outputs. Glucagon (0.1-10 mumol/kg) produced a bell-shaped dose-response curve for the secretory rate, bicarbonate and protein outputs. 3. The secretory activity of 30 nmol/kg of PHI corresponded roughly to that of 80 pmol/kg of secretin, 9 nmol/kg of VIP and 0.6 mumol/kg of glucagon, respectively. Thus, based on administered dose, PHI was about 375 x less potent than secretin, 3 x less potent than VIP and 20 x more potent than glucagon. 4. The PHI- and VIP-stimulated secretions were inhibited by a VIP antagonist, but not by a glucagon antagonist, SCH23390 (a dopamine D-1 antagonist), L-364718 (a cholecystokinin antagonist) or atropine. 5. Each peptide increased cyclic AMP concentration, but not cyclic GMP concentration, concomitant with the increase in pancreatic secretion. 6. From these results, it is concluded that PHI produces an increase in pancreatic secretion by acting on VIP-preferring receptors on the exocrine pancreatic gland of the dogs. This may be mediated at least in part through the increase of intracellular cyclic AMP concentrations.