Bombesin, a bioactive peptide first identified in amphibian skin, is related to two mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB). A family of 3 GPCRs, including NMB-R (BB1), GRP-R (BB2) and BRS-3 (BB3), mediate the biological effects of the peptides. The receptors differ in their affinities for the peptides; BB2 binds to GRP with 50-300-fold greater affinity than to NMB, whereas BB1 binds to NMB with 10-800-fold greater affinity than to GRP. Binding of ligand to BB1 activates Gq to increase intracellular calcium concentrations. The CNS is a major site of NMB and BB1 expression, and BB1 appears to be involved in thermoregulation.