Constitutive activity of the histamine H1 receptor reveals inverse agonism of histamine H1 receptor antagonists
Constitutive activity of the histamine H1 receptor reveals inverse agonism of histamine H1 receptor antagonists
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DOI：
10.1016/s0014-2999(99)00803-1
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发表时间：
2000-01-03
影响因子：
5
通讯作者：
Leurs, R
中科院分区：
文献类型：
--
作者：
Bakker, RA;Wieland, K;Leurs, R
野生型人组胺H-1受体在sv40永活的非洲绿猴肾细胞中的短暂表达导致第二信使肌醇三磷酸基础水平的不依赖于激动剂的升高。几种组胺H-1受体拮抗剂，包括治疗上使用的抗过敏西替利嗪、氯雷他定和爱司他汀，降低了这种组成组胺H-1受体的活性，逆激动作用，即稳定人类组胺H-1受体的非活性构象，因此可能是临床使用的抗组胺药抗过敏作用机制的关键组成部分。(C) 2000 Elsevier Science B.V.版权所有
Transient expression of the wild-type human histamine H-1 receptor in SV40-immortalised African green monkey kidney cells resulted in an agonist-independent elevation of the basal levels of the second messenger inositoltrisphospate. Several histamine H-1 receptor antagonists, including the therapeutically used anti-allergies cetirizine, loratadine and epinastine reduced this constitutive histamine H-1 receptor activity, inverse agonism, i.e., stabilisation of an inactive conformation of the human histamine H-1 receptor, may therefore be a key component of the anti-allergic mechanism of action of clinically used antihistamines. (C) 2000 Elsevier Science B.V. All rights reserved.