Molecular cloning and characterization of avian bombesin‐like peptide receptors: new tools for investigating molecular basis for ligand selectivity
2003; Wiley; Volume: 139; Issue: 3 Linguagem: Inglês
10.1038/sj.bjp.0705282
ISSN1476-5381
AutoresMaiko Iwabuchi, Kumiko Ui‐Tei, Kazuhiko Yamada, Yoichi Matsuda, Yasushi Sakai, Kohichi Tanaka, Hiroko Ohki‐Hamazaki,
Tópico(s)Receptor Mechanisms and Signaling
ResumoBombesin (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. 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 and synthetic bombesin agonist, [ D ‐Phe 6 , β ‐Ala 11 , Phe 13 , Nle 14 ]bombesin(6–14) ([FAFNl]BN(6–14)). The chGRP‐R gene was localized to chicken chromosome 1q23distal‐q24proximal, where chick homologs of other human X‐linked genes have also been mapped. 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. Expression of both receptors was detected in brain, but only chGRP‐R was expressed in gastrointestinal (GI) tissues. 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. 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. British Journal of Pharmacology (2003) 139 , 555–566. doi: 10.1038/sj.bjp.0705282
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