Bombesin receptor subtype mediation of gastroenteropancreatic hormone secretion in rats

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-Phe 6]bombesin(6–13)-methylester {[ d-Phe 6]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-Phe 6]Bn(6–13)OMe (1000 nmol/kg/h), or bombesin plus [ d-Phe 6]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 Blood was withdrawn from jugular vein catheters before and 30 min after the start of infusions.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-Phe 6]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-Phe 6]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.