文章基本信息

标题：Localization of a Novel Non-peptide Angiotensin II Type 1 Receptor Antagonist, E4177, in Rat Adrenal Glomerulosa
本地全文：下载
作者：Motoharu KAKIKI ; Toru HORIE
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1996
卷号：19
期号：10
页码：1357-1361
DOI：10.1248/bpb.19.1357
出版社：The Pharmaceutical Society of Japan
摘要：We investigated the distribution of a novel angiotensin II type 1 (AT1) receptor antagonist, E4177 (4'-[2-cyclopropyl-7-methyl-3H-imidazo[5, 4-b]pyridine-3-yl]methyl-2-biphenylcarboxylic acid), in rat adrenal glomerulosa. In a binding assay of adrenal capsular tissue (mainly glomerulosa), E4177 exhibited a maximum displacement of approximately 80% of total ¹²⁵I-labeled angiotensin II (¹²⁵I-[Sal¹, Ile⁸] Ang II) binding, and its IC₅₀ value was 6.9±0.5 nM. This IC₅₀ value indicated a slightly higher in vitro potency than that of losartan (21.0±0.6 nM). Also, in a receptor autoradiographic study, E4177 (10000 nM) displaced approximately 80% of radiolabeled ¹²⁵I-[Sal¹, Ile⁸] Ang II in rat adrenal glomerulosa and caused only slight displacement in rat adrenal medulla. Further, light and electron microscopic autoradiography of adrenal glomerulosa for 15 min after the intravenous administration of 1 mg/kg [¹⁴C]E4177, indicated the localization of ¹⁴C, possibly in the adrenal zona glomerulosa cell plasma membrane. It was strongly suggested that E4177 is a potent and selective antagonist of the AT1 receptor, and that it specifically binds to AT1 receptors in the adrenal zona glomerulosa.
关键词：angiotensin II type 1 receptor;E4177;autoradiography;losartan