Meal pattern analysis in rats reveals partial agonist activity of the bombesin receptor antagonist BW2258U89.

The spontaneous feeding behavior of adult male rats was monitored during continuous infusion of the bombesin receptor antagonist BW2258U89 into the coeliac artery (100 micrograms kg-1 h-1) from an osmotic minipump. Nocturnal food intake was suppressed over 5 days of testing. Similar effects followed acute BW2258U89 treatment [100 micrograms kg-1, intraperitoneally (i.p.)]. Moreover, i.p. BW2258U89 mimicked the acute behavioral effects of 2 micrograms kg-1 i.p. bombesin by reducing meal size. Verifying that BW2258U89 can retain its potency throughout the entire period of chronic infusion, we demonstrated that the acute anorectic action of bombesin (4 micrograms kg-1, i.p.) was blocked by pretreatment with a BW2258U89 solution (100 micrograms ml-1 kg-1, i.p.) that was freshly prepared, or incubated for 1 or 6 days at body temperature. These data demonstrate that acute and chronic administration of BW2258U89, at a dose that abolishes the satiety effect of bombesin, significantly suppresses spontaneous feeding. Thus, BW2258U89 appears to attenuate food intake by acting as a partial agonist at peripheral receptors for bombesin-like peptides.