Blockade of brain bombesin/GRP receptors increases food intake in satiated rats.

The mechanisms that initiate or terminate a meal remain obscure. Bombesin (BN) and gene-related peptides (GRP) have been reported to induce a satiety-like state in several species including fowl, mouse, rat, wolf, pig, baboon, and humans. The evolutionary conservation of this pharmacological response suggests a physiological role for the endogenous BN-like peptide(s) in the regulation of food intake. If the release of BN-like peptide(s) represents a "satiety signal" then pharmacological antagonism of this action should enhance food intake and/or postpone satiety. We report herein 1) that [Leu14, psi 13-14]-BN, a BN receptor antagonist, blocks the suppressive effect of centrally administered BN on food intake and 2) that in satiated rats, this pseudopeptide enhances food intake; the effects were more potent and efficacious upon the fourth compared with the third ventricular administration. These results support the contention that endogenous BN-like peptides mediate satiety and that this effect involves brain BN receptors in the caudal brain stem site(s).