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Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC‐21268
Author(s) -
Shinoura Hitomi,
Take Hitoshi,
Hirasawa Akira,
Inoue Kazuhide,
Ohno Yasuo,
Hashimoto Keitaro,
Tsujimoto Gozoh
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01079-6
Subject(s) - vasopressin receptor , radioligand , receptor , vasopressin , arginine vasopressin receptor 2 , medicine , endocrinology , amino acid , antagonist , arginine vasopressin receptor 1b , neuropeptide , receptor antagonist , chemistry , peptide , transmembrane domain , biology , biochemistry
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.