G-Protein–Coupled Receptors in Heart Disease. Issue 6 (31st August 2018)

• Record Type: Journal Article
• Authors: Wang, Jialu; Gareri, Clarice; Rockman, Howard A.
• Is Part Of: Circulation research. Volume 123:Issue 6(2018)
• Publication Date: 2018-08-31
• Subjects: arrestin -- bias -- coronary artery disease -- GPCR -- heart failure -- hypertension; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.118.311403
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : 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.