The bombesin-like peptides comprise a large family of peptides originally characterized in amphibians, then later found to be widely distributed in mammals. CNS administration of bombesin to rats has potent effects on appetite, body temperature, grooming, heart rate, and GI function. Two mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been characterized to date. At present, three mammalian bombesin-like peptide receptors have been characterized; the GRP receptor (also known as the bombesin BB2 receptor), the NMB receptor (also known as the BB1 receptor) and a third, orphan receptor whose ligand is unknown, designated the BRS-3 receptor or BB3 receptor. These known receptors cannot however explain all of bombesin's CNS effects - particularly bombesin's effects on body temperature and grooming. This suggests that other bombesin receptor subtypes remain to be characterized. Our laboratory has now characterized a receptor for amphibian bombesin and shown that it establishes a fourth class of bombesin receptors we have designated BB4. Using PCR, we have identified a mammalian homolog of the BB4 receptor in rat brain stem. This makes it likely that some of the functions of bombesin-like peptides in mammals are mediated by the BB4 receptor. Thus the purpose of this project is to characterize the structure, distribution and physiologic functions of the bombesin BB4 receptors. Because bombesin-like peptides occur in high levels in frogs; the frog is an ideal model for initial characterization of new bombesin-like peptides and receptors. In fact, to study the BB4 receptor, the frog model is necessary because though we have identified a partial cDNA encoding the mammalian BB4 receptor, the BB4 ligands have so far only been identified in frogs. The bombesin-BB4 receptor system is quite complex in that there are four subtypes of bombesin and, most likely, four cognate subtypes of the BB4 receptor. Thus our strategy is to first characterize the BB4 receptors in frogs, then use this information to guide our analysis of primate BB4 receptor(s).
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