A NOVEL BOMBESIN RECEPTOR ANTAGONIST SELECTIVELY BLOCKS THE SATIETY ACTION OF PERIPHERALLY ADMINISTERED BOMBESIN

To investigate the effect of a new, specific antagonist for bombesin receptors on the satiating action of exogenous bombesin, adult male rats were adapted to a nondeprivation test regimen with daily access to a palatable liquid food. In a prefeeding paradigm, rats received intraperitoneal injections of the bombesin receptor antagonist, BW2258U89 (6.25, 25, 50, or 100 mu g kg(-1)) or vehicle 20 min before, and then a second injection of either bombesin (4 mu g kg(-1)), gastrin-releasing peptide(l8-27) (GRP(18-27);16 mu mu gkg(-1)), the C-terminal octapeptide of cholecystokinin (CCK-8; 4 mu g kg(-1)), or vehicle 5 min before a 2-h feeding test. BW2258U89 pretreatment antagonized the satiating actions of bombesin and GRP18-27 in a very potent, dose-related manner, but did not antagonize the satiating action of CCK-8. These differential results with BW2258U89 are consistent with prior results showing the potency of this antagonist for bombesin receptor-mediated effects in visceral systems; in addition, they demonstrate the selectivity of the compound for the satiating actions of peripherally administered bombesin and bombesin-like peptides.