Bombesin, a bioactive peptide first identified in amphibian skin, is related to two mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B. A family of 3 GPCRs, including GRP-R (BB1), NMB-R (BB2) and BRS-3 (BB3), mediate the biological effects of the peptides. BB3 differs from the others by its low affinity for bombesin. Although an endogenous ligand for BB3 has yet to be identified, a synthetic nonselective bombesin-like peptide [D-Phe6, beta-Ala11, Phe13, Nle14]-bombesin-(6-14)-amide activates BB3 with high potency. BB3-null mice develop mild obesity that can be alleviated by treatment with an antiobesity compound, the serotonin and noradrenaline reuptake inhibitor Sibutramine.