EFFECTS OF POTENT BOMBESIN ANTAGONIST ON EXOCRINE PANCREATIC-SECRETION IN RATS

Recent synthesis of specific, potent bombesin receptor antagonists allows examination of the role of bombesin-like peptides in physiological processes in vivo. We characterized effects of [D-Phe6]bombesin(6-13)-methyl-ester (BME) on pancreatic enzyme secretion stimulated by the C-terminal decapeptide of gastrin releasing peptide (GRP-10), food intake, and diversion of bile-pancreatic juice in rats. In isolated pancreatic acini, BME had no agonistic effects on amylase secretion but competitively inhibited responses to GRP-10, yielding a pA2 value of 8.89 +/- 0.19. In conscious rats with gastric, jugular vein, bile-pancreatic, and duodenal cannulas, basal enzyme secretion (bile-pancreatic juice recirculated) was not affected by the antagonist. Maximal amylase response to GRP-10 (0.5 nmol/kg/h) was inhibited dose dependently by BME, reaching 97% inhibition at a dose of 400 nmol/kg/h. The dose response curve of amylase secretion stimulated by GRP-10 was shifted to the right by 40 nmol/kg/h BME, but maximal amylase response was unaltered, suggesting competitive inhibition in vivo. Liquid food intake and bile-pancreatic juice diversion caused substantial increases in amylase secretion; neither response was altered during administration of 400 pmol/kg/h BME. These results demonstrate that BME is a potent, competitive antagonist of pancreatic responses to bombesin-like peptides in vitro and in vivo. Lack of effect of BME on basal pancreatic secretion or responses to liquid food intake or diversion of bile-pancreatic juice in rats suggests that endogenous bombesin-like peptides do not act either directly or indirectly to mediate these responses.