Bombesin receptor subtype mediation of gastroenteropancreatic hormone secretion in rats

Gabor Varga, Thomas E. Adrian, David H. Coy, Roger D. Reidelberger

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Bombesin is a potent releaser of many gut and pancreatic hormones including gastrin, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP), cholecystokinin (CCK), enteroglucagon, and insulin. Three mammalian bombesin-like peptides, gastrin-releasing peptide (GRP), neuromedin C (NMC or GRP-10), and neuromedin B (NMB), and two bombesin receptor subtypes, GRP preferring and NMB preferring, have been characterized. We used a highly potent, selective antagonist of the GRP-preferring receptor, [d-Phe6]bombesin(6-13)-methylester {[d-Phe6]Bn(6-13)OMe}, to determine the receptor subtype mediating bombesin-induced secretion of gastrin, GIP, PP, peptide YY (PYY), and insulin, as well as the importance of endogenous bombesin-like peptides in controlling basal secretion of these hormones. Unanesthetized rats received femoral vein infusion of saline, bombesin (10 nmol/kg/h), [d-Phe6]Bn(6-13)OMe (1000 nmol/kg/h), or bombesin plus [d-Phe6]Bn(6-13)OMe. Blood was withdrawn from jugular vein catheters before and 30 min after the start of infusions. Plasma gastrin, GIP, PP, PYY, and insulin were measured by specific radioimmunoassays. [d-Phe6]Bn(6-13)OMe alone reduced basal insulin levels by 28% (p < 0.05) but did not alter basal levels of plasma PP, GIP, PYY, or gastrin (p > 0.05 for each). Bombesin infusion significantly increased plasma levels of each hormone (p < 0.0001 for each). [d-Phe6]Bn(6-13)OMe completely blocked bombesin-induced increases in PP, insulin, and gastrin, and almost completely blocked increases in GIP and PYY (p < 0.01 for each). Our results suggest that (a) exogenous bombesin significantly stimulates PP, insulin, GIP, PYY, and gastrin secretion, (b) bombesin-induced secretion of these hormones is primarily mediated by the GRP-preferring receptor, and (c) an endogenous bombesin-like peptide acting at this receptor subtype plays an important physiological role in control of basal secretion of insulin but not PP, GIP, PYY, or gastrin.

Original languageEnglish
Pages (from-to)713-718
Number of pages6
JournalPeptides
Volume15
Issue number4
DOIs
Publication statusPublished - 1994

Keywords

  • Gastrin-releasing peptide
  • Insulin
  • Radioimmunoassay
  • Receptor antagonist

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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