血管紧张素II
肾素-血管紧张素系统
受体
机制(生物学)
内生
血管紧张素受体
效应器
功能(生物学)
神经科学
信号转导
药理学
生物
计算生物学
生物信息学
医学
细胞生物学
内科学
血压
哲学
认识论
作者
Ulrike Muscha Steckelings,Robert E Widdop,Edward D. Sturrock,Lizelle Lubbe,Tahir Hussain,Elena Kaschina,Thomas Unger,Anders Hallberg,Robert M. Carey,Colin Sumners
出处
期刊:Pharmacological Reviews
[American Society for Pharmacology & Experimental Therapeutics]
日期:2022-09-30
卷期号:74 (4): 1051-1135
被引量:22
标识
DOI:10.1124/pharmrev.120.000281
摘要
Discovered more than 30 years ago, the angiotensin AT2 receptor (AT2R) has evolved from a binding site with unknown function to a firmly established major effector within the protective arm of the renin-angiotensin system (RAS) and a target for new drugs in development. The AT2R represents an endogenous protective mechanism that can be manipulated in the majority of preclinical models to alleviate lung, renal, cardiovascular, metabolic, cutaneous, and neural diseases as well as cancer. This article is a comprehensive review summarizing our current knowledge of the AT2R, from its discovery to its position within the RAS and its overall functions. This is followed by an in-depth look at the characteristics of the AT2R, including its structure, intracellular signaling, homo- and heterodimerization, and expression. AT2R-selective ligands, from endogenous peptides to synthetic peptides and nonpeptide molecules that are used as research tools, are discussed. Finally, we summarize the known physiological roles of the AT2R and its abundant protective effects in multiple experimental disease models and expound on AT2R ligands that are undergoing development for clinical use. The present review highlights the controversial aspects and gaps in our knowledge of this receptor and illuminates future perspectives for AT2R research. SIGNIFICANCE STATEMENT: The angiotensin AT2 receptor (AT2R) is now regarded as a fully functional and important component of the renin-angiotensin system, with the potential of exerting protective actions in a variety of diseases. This review provides an in-depth view of the AT2R, which has progressed from being an enigma to becoming a therapeutic target.
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