RRC ID 41791
著者 Inada Y, Nakane T, Chiba S.
タイトル Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors.
ジャーナル Fundam Clin Pharmacol
Abstract We studied the binding properties of KRH-594, a new selective antagonist of angiotensin II (AII) type 1 (AT1) receptors, to rat liver membranes and to recombinant AT1 and AT2 receptors. Preincubation of rat liver membranes with KRH-594 produced maximal inhibition of [125I]-AII binding when the preincubation time was 1-2 h. Preincubation with KRH-594 for 2 h decreased the B(max) value and increased the Kd value. For human AT1, human AT2, rat AT1A and rat AT1B receptors, the Ki values for KRH-594 were 1.24, 9360, 0.67, and 1.02 nm, respectively. The rank order of K1 values for human AT1 receptors was KRH-594 > EXP3174 > candesartan = AII. The order of specificities for human AT1 and AT2 receptors was candesartan > EXP3174 > KRH-594. Although a 2-h preincubation of human AT2 receptors with KRH-594 (30 microM) or CGP 42112 (a selective AT2 receptor antagonist; 0.3 nM) inhibited binding of [125I]-AII, the suppression by KRH-594 was not significant. These results indicate that KRH-594 binds potently to AT1 receptors in an insurmountable manner, and that at a very high dose (30 microM) it may also bind to AT2 receptors, but in a surmountable manner.
巻・号 16(4)
ページ 317-23
公開日 2002-8-1
DOI 10.1046/j.1472-8206.2002.00076.x
PMID 12570021
MeSH Angiotensin II / antagonists & inhibitors* Angiotensin Receptor Antagonists* Animals Benzimidazoles / pharmacology Biphenyl Compounds COS Cells Chlorocebus aethiops Dose-Response Relationship, Drug Humans Imidazoles / pharmacology In Vitro Techniques Liver / drug effects Liver / metabolism Losartan / pharmacology Membranes Oligopeptides / pharmacology Radioligand Assay Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin / genetics Receptors, Angiotensin / metabolism Tetrazoles / pharmacology* Thiadiazoles / pharmacology* Time Factors Transfection
IF 2.754
引用数 4
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 COS-7(RCB0539)