Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark (U.M.S.); Cardiovascular Disease Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (R.E.W.); Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Republic of South Africa (E.D.S., L.L.); Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas (T.H.); Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pharmacology, Cardiovascular-Metabolic-Renal (CMR) Research Center, DZHK (German Centre for Cardiovascular Research), Berlin, Germany (E.K.); CARIM - School for Cardiovascular Diseases, Maastricht University, The Netherlands (T.U.); Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden (A.H.); Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia (R.M.C.); and Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida (C.S.)
Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark (U.M.S.); Cardiovascular Disease Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (R.E.W.); Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Republic of South Africa (E.D.S., L.L.); Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas (T.H.); Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pharmacology, Cardiovascular-Metabolic-Renal (CMR) Research Center, DZHK (German Centre for Cardiovascular Research), Berlin, Germany (E.K.); CARIM - School for Cardiovascular Diseases, Maastricht University, The Netherlands (T.U.); Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden (A.H.); Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia (R.M.C.); and Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida (C.S.).
Pharmacol Rev. 2022 Oct;74(4):1051-1135. doi: 10.1124/pharmrev.120.000281.
Discovered more than 30 years ago, the angiotensin AT receptor (ATR) 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 ATR 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 ATR, 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 ATR, including its structure, intracellular signaling, homo- and heterodimerization, and expression. ATR-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 ATR and its abundant protective effects in multiple experimental disease models and expound on ATR 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 ATR research. SIGNIFICANCE STATEMENT: The angiotensin AT receptor (ATR) 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 ATR, which has progressed from being an enigma to becoming a therapeutic target.
三十多年前发现的血管紧张素 AT 受体（ATR）已从具有未知功能的结合位点演变为肾素-血管紧张素系统（RAS）中牢固确立的主要效应器，也是开发新药的靶点。ATR 代表了一种内源性保护机制，在大多数临床前模型中都可以对其进行操作，以缓解肺部、肾脏、心血管、代谢、皮肤和神经疾病以及癌症。本文全面综述了 ATR 的最新知识，从其发现到在 RAS 中的位置及其整体功能。接下来深入探讨了 ATR 的特征，包括其结构、细胞内信号转导、同源和异源二聚化以及表达。讨论了 ATR 选择性配体，从内源性肽到用于研究的合成肽和非肽分子。最后，我们总结了 ATR 的已知生理作用及其在多种实验疾病模型中的丰富保护作用，并阐述了正在开发用于临床应用的 ATR 配体。本综述强调了该受体的知识存在争议和空白的方面，并阐明了 ATR 研究的未来前景。
血管紧张素 AT 受体（ATR）现在被认为是肾素-血管紧张素系统的一个功能齐全且重要的组成部分，具有在多种疾病中发挥保护作用的潜力。该综述深入探讨了 ATR，它已从一个谜发展成为一个治疗靶点。
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