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Mechanisms and functions of agonist-independent activation in the angiotensin II type 1 receptor.

Abstract：

:The angiotensin II (AngII) type 1 (AT(1)) receptor is a seven-transmembrane G protein-coupled receptor, and is involved in regulating the physiological and pathological process of the cardiovascular system. Systemically and locally generated AngII has agonistic action on AT(1) receptor, but recent studies have demonstrated that AT(1) receptor inherently shows spontaneous activity even in the absence of AngII. Furthermore, mechanical stress can activate AT(1) receptor by inducing conformational switch without the involvement of AngII, and induce cardiac hypertrophy in vivo. These agonist-independent activities of AT(1) receptor can be inhibited by inverse agonists, but not by neutral antagonists. Considerable attention has been directed to molecular mechanisms and clinical implications of agonist-independent AT(1) receptor activation, and inverse agonist activity emerges as an important pharmacological parameter for AT(1) receptor blockers that will improve efficacy and expand therapeutic potentials in cardiovascular medicine.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Akazawa H,Yasuda N,Komuro I

doi

10.1016/j.mce.2008.11.007

subject

Has Abstract

pub_date

2009-04-29 00:00:00

pages

140-7

issue

2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(08)00541-8

journal_volume

302

pub_type

杂志文章,评审

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