title: Effects of potent bombesin antagonist on exocrine pancreatic secretion in rats.
abstract: 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.
authors.affiliation: Department of Medicine, Kansas University Medical Center, Kansas City 66103.
authors.forename: G
authors.initials: G
authors.lastname: Varga
authors.forename: R D
authors.initials: RD
authors.lastname: Reidelberger
authors.forename: R M
authors.initials: RM
authors.lastname: Liehr
authors.forename: L J
authors.initials: LJ
authors.lastname: Bussjaeger
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
authors.forename: T E
authors.initials: TE
authors.lastname: Solomon
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D015904:Biliopancreatic Diversion; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004435:Eating; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; C071101:bombesin (6-13), Phe(6) methyl ester-; C040794:neuromedin C; D000681:Amylases; D001839:Bombesin