Amphibian bombesin and its related peptides consist a family of neuropeptides in many vertebrate species. Bombesin and two major bombesin-like peptide in mammals, gastrinreleasing peptide (GRP) and neuromedin B (NMB), have been shown to elicit various physiological effects. These include inhibition of feeding, smooth muscle contraction, exocrine and endocrine secretions, thermoregulation, blood pressure and sucrose regulations and cell growth. Receptors for GRP and NMB (GRP-R and NMB-R), as well as third subtype of bombesin-like peptide receptor (BRS-3) have been cloned. These receptors are G-protein-coupled receptors and are expressed in various brain regions and in the digestive tract. In this paper, we will summarize studies on these peptides and their receptors, with special reference to research using gene-knockout mice. These studies clearly demonstrated the role of three receptors in vivo and in vitro. We will also discuss the phylogeny of these receptors. KEY WORDS: gastrin-releasing peptide, neuromedin B, bombesin-like peptide receptor subtype-3 (BRS-3)Int.

1 Bombesin (BN), originally isolated from amphibians, is structurally related to a family of BN-like peptides found in mammals, which include gastrin-releasing peptide (GRP) and neuromedin B (NMB). These peptides have important effects on secretion, smooth muscle contraction, metabolism and behavior. Here we report cloning and characterization of two subtypes of BN-like peptide receptors in Aves. 2 The amino-acid sequence of chick GRP-R (chGRP-R) is highly identical with mammalian and amphibian GRP-R, and this receptor showed high affinity for GRP, BN (6 -14)). The chGRP-R gene was localized to chicken chromosome 1q23distal-q24proximal, where chick homologs of other human Xlinked genes have also been mapped. 3 ChBRS-3.5, having sequence similarities to both mammalian bombesin-like peptide receptor subtype-3 and amphibian bombesin-like peptide receptor subtype-4, showed high affinity for [FAFNl]BN(6 -14), moderate affinity for BN, but low affinity for both GRP and NMB. 4 Expression of both receptors was detected in brain, but only chGRP-R was expressed in gastrointestinal (GI) tissues. 5 When expressed in Chinese hamster ovary K1 cells, these receptors mediate intracellular calcium mobilization upon agonist stimulation. These results suggest that a novel BN peptide may occur in Aves as an endogenous ligand for chBRS-3.5. 6 The receptor sequences responsible for ligand selectivities were discussed and this knowledge about avian BN-like peptide receptors will help us to understand the molecular basis for agonist sensitivities of BN-like peptide receptors.

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