G-Protein–Coupled Receptors in Heart Disease

Abstract

<p class="first" id="P1">G protein-coupled receptors (GPCRs) play a central physiological role in the regulation of cardiac function in both health and disease and thus represents one of the largest class of surface receptors targeted by drugs. Several antagonists of GPCRs, such as β adrenergic receptors and 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. While the mechanism of action for GPCRs was thought to be largely worked-out in the 1980’s and 90’s, 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 of such as ligand bias, β-arrestin-mediated signaling, and conformational heterogeneity. </p>