BOMBESIN RECEPTOR SUBTYPE MEDIATION OF GASTROENTEROPANCREATIC HORMONE-SECRETION IN RATS

Bombesin is a potent releaser of many gut and pancreatic hormones incl uding gastrin, glucose-dependent insulinotropic polypeptide (GIP), pan creatic polypeptide (PP), cholecystokinin (CCK), enteroglucagon, and i nsulin. Three mammalian bombesin-like peptides, gastrin-releasing pept ide (GRP), neuromedin C (NMC or GRP-10), and neuromedin B (NMB), and t wo 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 bombe sin-induced secretion of gastrin, GIP, PP, peptide YY (PYY), and insul in, as well as the importance of endogenous bombesin-like peptides in controlling basal secretion of these hormones. Unanesthetized rats rec eived 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)O Me. Blood was withdrawn from jugular Vein catheters before and 30 min after the start of infusions. Plasma gastrin, GIP, PP, PW, and insulin were measured by specific radioimmunoassays. [D-Phe(6)]Bn(6-13)OMe al one reduced basal insulin levels by 28% (p < 0.05) but did not alter b asal levels of plasma PP, GIP, PW, or gastrin (p > 0.05 for each). Bom besin infusion significantly increased plasma levels of each hormone ( p < 0.0001 for each). [o-Phe(6)]Bn(6-13)OMe completely blocked bombesi n-induced increases in PP, insulin, and gastrin, and almost completely blocked increases in GIP and PYY (p < 0.01 for each). Our results sug gest that (a) exogenous bombesin significantly stimulates PP, insulin, GIP, PYY, and gastrin secretion, (b) bombesin-induced secretion of th ese hormones is primarily mediated by the GRP-preferring receptor, and (c) an endogenous bombesin-like peptide acting at this receptor subty pe plays an important physiological role in control of basal secretion of insulin but not PP, GIP, PYY, or gastrin.