From the Department of Medicine (J.W., C.G., H.A.R.).
Department of Cell Biology (H.A.R.).
Circ Res. 2018 Aug 31;123(6):716-735. doi: 10.1161/CIRCRESAHA.118.311403.
GPCRs (G-protein [guanine nucleotide-binding protein]-coupled receptors) play a central physiological role in the regulation of cardiac function in both health and disease and thus represent one of the largest class of surface receptors targeted by drugs. Several antagonists of GPCRs, such as βARs (β-adrenergic receptors) and Ang II (angiotensin II) receptors, are now considered standard of therapy for a wide range of cardiovascular disease, such as hypertension, coronary artery disease, and heart failure. Although the mechanism of action for GPCRs was thought to be largely worked out in the 80s and 90s, recent discoveries have brought to the fore new and previously unappreciated mechanisms for GPCR activation and subsequent downstream signaling. In this review, we focus on GPCRs most relevant to the cardiovascular system and discuss traditional components of GPCR signaling and highlight evolving concepts in the field, such as ligand bias, β-arrestin-mediated signaling, and conformational heterogeneity.
G 蛋白偶联受体（GPCRs）在调节健康和疾病中的心脏功能方面发挥着核心生理作用，因此是药物靶向的最大表面受体之一。目前，几种 GPCR 拮抗剂，如βARs（β-肾上腺素能受体）和 Ang II（血管紧张素 II）受体，被认为是治疗多种心血管疾病的标准药物，如高血压、冠心病和心力衰竭。尽管 GPCR 的作用机制在 80 年代和 90 年代就已经被广泛研究，但最近的发现揭示了 GPCR 激活和随后的下游信号转导的新的和以前未被重视的机制。在这篇综述中，我们重点介绍与心血管系统最相关的 GPCR，并讨论 GPCR 信号转导的传统成分，并强调该领域的新兴概念，如配体偏向、β-arrestin 介导的信号转导和构象异质性。
