BOMBESIN RECEPTOR ANTAGONISTS BLOCK THE EFFECTS OF EXOGENOUS BOMBESINBUT NOT OF NUTRIENTS ON FOOD-INTAKE

The endogenous, meal-contingent release of bombesin (BN)-like peptides is thought to contribute to the termination of a meal. In the followi ng experiments the potency of BN receptor antagonists to attenuate the ability of nutrients to suppress food intake was tested. First, the e ffectiveness of BN receptor subtype antagonists was verified by testin g their ability to block the effects of exogenous BN on food intake. R ats were administered intraperitoneal (i.p.) injections of either sali ne or 0.1 mg/kg [D-Phe(12),Leu(14)]BN (binds both GRP and NMB receptor s), [D-Phe(6)]BN(6-13) ethyl amide (binds GRP > NMB), and cyclo-SS-oct a (BIM-23042; binds NMB > GRP). Five minutes later rats were administe red 8 mu g/kg BN (i.p.) and milk intake was measured. Injections of [D -Phe(12),Leu(14)]BN and [D-Phe(6)]BN(6-13) ethyl amide reliably attenu ated the ability of BN to suppress milk intake whereas BIM-23042 was i neffective. The results show that the antagonists were behaviorally ef fective and that exogenous BN may exert its effects on food intake pri marily through the GRP receptor subtype. Next, the antagonists were ad ministered either 5 min prior to or 5 min after an intragastric nutrie nt load or no load in both overnight-deprived and nondeprived rats, an d milk intake was then measured. Stomach loads reduced intake and this effect was not attenuated by BN receptor antagonists. Finally, rats w ere allowed to prefeed and the milk was then removed. Rats were then a dministered a BN receptor antagonist (0.1 and 1.0 mg/kg) or saline eit her immediately after the prefeed, 10 min later, or 20 min later. Milk diet was then returned and intake was measured. Peripheral injections of the BN receptor antagonist had no effect compared to saline on mil k intake. Collectively, the results indicate that the blockade of peri pheral BN peptide receptors is not sufficient to attenuate the satiety signals generated by stomach loads or prefeeding. (C) 1997 Elsevier S cience Inc.