Effect of L-364,718 on GRP-Stimulated Pancreatic and Gastric Secretions and GI Peptides in Conscious Dogs

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Abstract
The effect of L-364,718, a cholecystokinin (CCK) receptor antagonist, on exocrine pancreatic secretion, gastric secretion, and plasma levels of gastrointestinal (G1) peptides stimulated by gastrin-releasing peptide (GRP) was examined in five conscious dogs. Intravenous infusion of graded doses of synthetic porcine GRP (18,36, and 178 pmol/kg/h) caused significant and dose-dependent increases in pancreatic and gastric juice secretion and in plasma levels of pancreatic polypeptide (PP), CCK, and gastrin. Intravenous injection of L-364,718 (20 nmol/kg) significantly inhibited GRP-stimulated pancreatic outputs of juice volume, protein, and amylase and plasma PP release. L-364,718 however, did not affect gastric juice volume and plasma levels of CCK and gastrin. The results suggest that endogenously released CCK is, at least in part, responsible for GRP-stimulated pancreatic protein and enzyme secretions and PP release in dogs. The results further suggest that GRP-stimulated pancreatic secretion might be, in part, a direct response of GRP to exocrine pancreas.

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