Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC‐21268

FEBS Letters

Ohno, Yasuo¹  Take, Hitoshi²  Hirasawa, Akira²  Inoue, Kazuhide¹  Tsujimoto, Gozoh²  Shinoura, Hitomi²  Hashimoto, Keitaro³ 

[1] Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo 158-8501, Japan;Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-Ku, Tokyo 154-8509, Japan;Department of Pharmacology, Yamanashi Medical College, Yamanashi 409-38, Japan

关键词: OPC-21268;    Vasopressin V1a receptor;    Species difference;    Chimeric receptor;    AVP;    arginine vasopressin;    TMD;    transmembrane domain;    ICL;    intracellular loop;    ECL;    extracellular loop;    CR;    chimeric receptor;   

DOI  :  10.1016/S0014-5793(00)01079-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A non-peptide, vasopressin V1a receptor-selective antagonist, OPC-21268, exhibited a markedly higher affinity for the rat V1a receptor (K _i=380 nM) than for the human V1a receptor (K _i=140 μM). To delineate the region responsible for the high affinity binding of OPC-21268 for the rat V1a receptor, we have constructed a series of chimeric human and rat V1a receptors, and examined the chimeric and point-mutated receptors by competitive radioligand binding analysis. The results showed that the transmembrane domain (TMD) VI–VII of the vasopressin V1a receptor, in particular the amino acid residue Ala-342 in TMD VII, is the major component conferring the rat-selective binding of OPC-21268 to the V1a receptor.

【 授权许可】

Unknown