Receptor subtype mediation of feeding suppression by bombesin-like peptides

Bombesin (BN) and the related mammalian peptides gastrin-releasing peptide (GRP), neuromedin C (NMC), and neuromedin B (NMB) suppress food intake in rats. Recent studies show two distinct receptor subtypes, GRP-preferring and NMB-preferring. BN interacts equally with both subtypes raising the possibility that one or both subtypes mediate the reduction of feeding by BN. To examine this issue, we compared suppression of intake produced by dose ranges (0-100 nmol/kg) of BN, GRP, NMC, and NMB and acetylated NMC and NMB. We found that all peptides elicited dose-dependent reductions of intake with overall differences in potency and efficacy. At intermediate doses, the rank order of potency for suppression was BN = AcNMC > NMC = GRP > NMB = AcNMB; however BN, GRP, and NMC were equipotent at the lowest and highest doses. Coadministration of NMC or GRP and NMB produced suppressions above that of either peptide alone and equivalent to BN. Taken together, these data support a role for both receptor subtypes in the suppression of food intake by BN and BN-like peptides.