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 micrograms kg-1) or vehicle 20 min before, and then a second injection of either bombesin (4 micrograms kg-1), gastrin-releasing peptide (GRP; 16 micrograms kg-1), the C-terminal octapeptide of cholecystokinin (CCK-8; 4 micrograms 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.