Molecular analysis of angiontensin II receptor inactivation by inverse agonists

血管紧张素Ⅱ（AngII）1型（AT_1）受体与其他机械敏感分子相互作用，提示AT_1受体在机械感觉中的相互作用具有功能相关性。反相激动剂和AT_1受体之间的多价相互作用协同稳定受体处于非活性构象，以响应AngII非依赖性激活的不同过程。即使在体内，当心脏中AT_1受体上调时，AT_1受体的组成性活性也不依赖于AngII而参与心脏重构，并且AT_1受体阻断剂的反向激动在预防由AT_1受体的组成性活性诱导的心脏重构中提供了治疗作用。

Angiotensin II (AngII) type 1 (AT_1) receptor physically interacts with other mechanosensitive molecules, which implicates functional relevance of the mutual interactions in mechanosensation by AT_1 receptor. Multivalent interactions between an inverse agonist and the AT_1 receptor cooperate to stabilize the receptor in an inactive conformation in response to the distinct processes of AngII-independent activation. Constitutive activity of AT_1 receptor contributes to cardiac remodeling independently of AngII even in vivo, when AT_1 receptor is up-regulalted in the heart, and inverse agonism of AT_1 receptor blockers provides therapeutic effects in the prevention of cardiac remodeling induced by constitutive activity of AT_1 receptor.