期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 458, 期 3, 页码 257-262出版社
ELSEVIER
DOI: 10.1016/S0014-2999(02)02819-4
关键词
sanguinarine; angiotensin AT(1) receptor; CHO cell; CHO membrane; noncompetitive atagonist; [H-3]candesartan
The type of interaction of 5-methyl-2,3,7,8-bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated from the root of Bocconia frutescens L., with the human angiotensin AT, receptor was evaluated in both intact cells and membrane binding of [3 H] (2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid) ([H-3]candesartan). The results indicate that the inhibition of [3H]candesartan binding by sanguinarine is independent of cell viability, since the alkaloid inhibited at a similar extent radioligand binding on both intact Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1) receptor (hAT(1)) and their cell membranes (K-i = 0.14 and 1.10 muM, respectively). The unsuccessful recovery of [3H]candesartan binding after washing sanguinarine off the cells suggested a nearly irreversible or slow reversible interaction. Saturation binding studies showed a substantial reduction of the B-max without affecting the K-d. In addition, the presence of 2-n-butyl-4chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole (losartan) could not prevent sanguinarine inhibition of [H-3]candesartan binding neither: The present. findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner. (C) 2002 Elsevier Science B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据