Identification of a domain of ETA receptor required for ligand binding

FEBS Letters

Yang, Yan-Yan²  Trzeciak, Arnold¹  Adachi, Miki²  Furuichi, Yasuhiro²  Miyamoto, Chikara² 

[1] Department of Pharma Research New Technologies, F. Hoffmann-La Roche & Co., Ltd., CH-4002, Basel, Switzerland;Department of Molecular Genetics, Nippon Roche Research Center, Kamakura 247, Japan

关键词: Endothelin (ET);    Receptor;    Binding site;    Ca2+ mobilization;    Expression;    Antagonist;    ET;    endothelin;    [Ca2+]i;    intracellular calcium concentration;    CHAPS;    3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate;    DMEM;    Dulbecco Modified Eagle Medium;    HEPES;    N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid;    CHO cells;    chinese hamster ovary cells;    Fura-2;    Fura-2-penta-acetoxymethyl ester;   

DOI  :  10.1016/0014-5793(92)81393-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Various chimeric ET_A and ET_B receptors were produced in CHO cells for the elucidation of a specific domain which influences the affinity of the receptor toward BQ-123, a selective ET_A antagonist. Replacement of the first extracellular loop domain (B-loop) of the ET_A receptor with the corresponding domain of the ET_B receptor, reduced the inhibition by BQ-123 drastically, while the replacements of other extracellular domains of ET_A did not. By contrast, the introduction of the B-loop of ET_A in place of the corresponding domain of the ET_B receptor endowed the ET_B-based chimeric receptor with a sensitivity to BQ-123. These observations suggest that the B-loop domain of the ET_A receptor is involved in ligand binding.

【 授权许可】

Unknown