$\beta$-Adrenergic receptor, an essential target in cardiovascular diseases
Heart Failure Reviews, (Aug 13, 2019)DOI: 10.1007/s10741-019-09825-x
Abstract
$\beta$-Adrenergic receptors ($\beta$ARs) belong to a large family of cell surface receptors known as G protein--coupled receptors (GPCRs). They are coupled to Gs protein (G$\alpha$s) for the activation of adenylyl cyclase (AC) yielding cyclic AMP (CAMP), and this provides valuable responses, which can affect the cardiac function such as injury. The binding of an agonist to $\beta$AR enhances conformation changes that lead to the G$\alpha$s subtype of heterotrimeric G protein which is the AC stimulatory G protein for activation of CAMP in the cells. However, cardiovascular diseases (CVD) have been reported as having an increased rate of death and $\beta$1AR, and $\beta$2AR are a promising tool that improves the regulatory function in the cardiovascular system (CVS) via signaling. It increases the G$\alpha$ level, which activates $\beta$AR kinase ($\beta$ARK) that affects and enhances the progression of heart failure (HF) through the activation of cardiomyocyte $\beta$ARs. We also explained that an increase in GPCR kinases (GRKs) would practically improve the HF pathogenesis and this occurs via the desensitization of $\beta$ARs, which causes the loss of contractile reserve. The consistency or overstimulation of catecholamines contributes to CVD such as stroke, HF, and cardiac hypertrophy. When there is a decrease in catecholamine responsiveness, it causes aging in old people because the reduction of $\beta$AR sensitivity and density in the myocardium enhances downregulation of $\beta$ARs to AC in the human heart.