TY - JOUR
T1 - Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC-21268
AU - Shinoura, Hitomi
AU - Take, Hitoshi
AU - Hirasawa, Akira
AU - Inoue, Kazuhide
AU - Ohno, Yasuo
AU - Hashimoto, Keitaro
AU - Tsujimoto, Gozoh
N1 - Funding Information:
This investigation was partially supported by research grants from the Scientific Fund of the Ministry of Education, Science and Culture of Japan, the Japan Health Science Foundation, the Ministry of Human Health and Welfare, and the Organized Research Combination System from the Science and Technology Agency.
PY - 2000/1/28
Y1 - 2000/1/28
N2 - 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. (C) 2000 Federation of European Biochemical Societies.
AB - 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. (C) 2000 Federation of European Biochemical Societies.
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U2 - 10.1016/S0014-5793(00)01079-6
DO - 10.1016/S0014-5793(00)01079-6
M3 - Article
C2 - 10682838
AN - SCOPUS:0033957635
SN - 0014-5793
VL - 466
SP - 255
EP - 258
JO - FEBS Letters
JF - FEBS Letters
IS - 2-3
ER -