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 that we have designated BB4. Using the amphibian BB4 receptor cDNA, we have screened a variety of rodent, human and monkey cDNA libraries for a mammalian homolog. To date, the analog has not yet been identified. However, in monitoring the EST database, we discovered a new receptor related to both the bombesin and endothelin receptors. We have designated this receptor as EL1. We have also discovered a second related subtype that we have designated as EL2. EL1 and EL2 are highly expressed in CNS. Studies are ongoing to begin to discover the function of