GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs regulate nearly every aspect of human physiology and disease, thus serving as important drug targets in cardiovascular disease. Sharing a conserved structure comprised of 7 transmembrane α-helices, GPCRs couple to heterotrimeric G-proteins, GPCR kinases, and β-arrestins, promoting downstream signaling through second messengers and other intracellular signaling pathways. GPCR drug development has led to important cardiovascular therapies, such as antagonists of β-adrenergic and angiotensin II receptors for heart failure and hypertension, and agonists of the glucagon-like peptide-1 receptor for reducing adverse cardiovascular events and other emerging indications. There continues to be a major interest in GPCR drug development in cardiovascular and cardiometabolic disease, driven by advances in GPCR mechanistic studies and structure-based drug design. This review recounts the rich history of GPCR research, including the current state of clinically used GPCR drugs, and highlights newly discovered aspects of GPCR biology and promising directions for future investigation. As additional mechanisms for regulating GPCR signaling are uncovered, new strategies for targeting these ubiquitous receptors hold tremendous promise for the field of cardiovascular medicine.

中文翻译：

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G 蛋白偶联受体：一个世纪的研究和发现。


GPCR（G 蛋白偶联受体），也称为 7 跨膜结构域受体，是人类基因组中最大的受体家族，拥有约 800 个成员。 GPCR 几乎调节人类生理和疾病的各个方面，因此可以作为心血管疾病的重要药物靶点。 GPCR 具有由 7 个跨膜 α 螺旋组成的保守结构，可与异三聚体 G 蛋白、GPCR 激酶和 β-抑制蛋白偶联，通过第二信使和其他细胞内信号传导途径促进下游信号传导。 GPCR 药物的开发带来了重要的心血管疗法，例如用于治疗心力衰竭和高血压的 β-肾上腺素能和血管紧张素 II 受体拮抗剂，以及用于减少不良心血管事件和其他新兴适应症的胰高血糖素样肽-1 受体激动剂。由于 GPCR 机制研究和基于结构的药物设计的进步，人们对心血管和心脏代谢疾病领域的 GPCR 药物开发仍然抱有浓厚的兴趣。这篇综述回顾了 GPCR 研究的丰富历史，包括临床使用的 GPCR 药物的现状，并强调了 GPCR 生物学的新发现以及未来研究的有希望的方向。随着调节 GPCR 信号传导的其他机制的被发现，针对这些普遍存在的受体的新策略为心血管医学领域带来了巨大的希望。