Angiotensin Receptors: Structure, Function, Signaling and Clinical Applications

Abstract

Angiotensinogen -a serpin family protein predominantly produced by the liver is systematically processed by proteases of the Renin Angiotensin system (RAS) generating hormone peptides. Specific cell surface receptors for at least three distinct angiotensin peptides produce distinct cellular signals that regulate system-wide physiological response to RAS. Two well characterized receptors are angiotensin type 1 receptor (AT1 receptor) and type 2 receptor (AT2 receptor).They respond to the octapeptide hormone angiotensin II. The oncogene product MAS is a putative receptor for Ang (1-7). While these are G-protein coupled receptors (GPCRs), the in vivo angiotensin IV binding sites may be type 2 trans-membrane proteins. These four receptors together regulate cardiovascular, hemodynamic, neurological, renal, and endothelial functions; as well as cell proliferation, survival, matrix-cell interactions and inflammation. Angiotensin receptors are important therapeutic targets for several diseases. Thus, researchers and pharmaceutical companies are focusing on drugs targeting AT1 receptor than AT2 receptor, MAS and AngIV binding sites. AT1 receptor blockers are the cornerstone of current treatment for hypertension, heart failure, renal failure and many types of vascular diseases including atherosclerosis, aortic aneurism and Marfan syndrome.

The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer

“…Furthermore, ACEIs do not interfere with the conversion of angiotensin-I to angiotensin-1-9 because they are converted by endopeptidases. After conversion to angiotensin-1-9, it is cleaved by ACE-2, which seems unaffected by classical ACEI, to become angiotensin-1-7, which binds to MAS receptors, causing the opposite effect of AT1R (vasodilatation, apoptosis, antiproliferation) (62)(63)(64)(65)(66). Currently, there are many ACEIs in existence in addition to captopril: enalapril, benazepril, and fosinopril and others.…”

COVID-19 and the renin-angiotensin system (RAS): A spark that sets the forest alight?

“…When Ang (1–7) binds to MAS receptors, it causes vasodilation, natriuresis, diuresis, and also exerts anti-proliferative and anti-inflammatory effects. This arm of the pathway constitutes the so-called “protective pathway” of the RAS as the effects are believed to be physiologically favourable [2] , [3] .…”

“…The RAS appears to be important in a number of pathological processes. AngII/AT1 activation leads to a number of unfavorable effects, which include vasoconstriction and hypertension, cellular differentiation and growth, endothelial dysfunction, and the formation of reactive oxidative species (ROS) that may ultimately lead to organ damage [2] , [3] , [4] . The vasodilator nitric oxide (NO) is released when Ang (1–7) binds to MAS and AT2 receptors [5] .…”

Corona Virus Disease 2019 (COVID-19) as a System-Level Infectious Disease With Distinct Sex Disparities

“…Of particular interest, SARS-CoV-2 interacts with the RAS via ACE2, which was also identified as a functional receptor for Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV) ( 7 – 9 ). It has been indicated that RAS activation during SARS-CoV-2 infection leads to a number of unfavorable effects, which include vasoconstriction and hypertension, cellular differentiation and growth, endothelial dysfunction, and the formation of Reactive Oxidative Species (ROS) that may ultimately lead to organ damage ( 10 , 11 ).…”