HINDBRAIN GRP RECEPTOR BLOCKADE ANTAGONIZES FEEDING SUPPRESSION BY PERIPHERALLY ADMINISTERED GRP

Bombesin (BN)-like peptides injected peripherally or centrally suppres s food intake in rats. The relationship between the central and periph eral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding eff ects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist; [D-F-5,Phe(6),D-Ala(11)]BN-(6-13)methyl est er (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produ ced by intraperitoneal administration of GRP-(18-27) in 5-h food-depri ved male Sprague-Dawley rats (n = 10). We found that fourth ventricula r administration of 10, 32, and 100 ng BN-ME blocked the suppression o f glucose intake produced by peripherally administered 10 nmol/kg GRP- (18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate-th at the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.