Sanket Patel1, Tahir Hussain2. 1. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Health 2, Room 3046, 4849 Calhoun Street, Houston, TX, 77204-5000, USA. 2. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Health 2, Room 3046, 4849 Calhoun Street, Houston, TX, 77204-5000, USA. thussain@central.uh.edu.
Abstract
PURPOSE OF REVIEW: Angiotensin type 2 receptor (AT2R) and receptor Mas (MasR) are part of the "protective arm" of the renin angiotensin system. Gene and pharmacological manipulation studies reveal that AT2R and MasR are involved in natriuretic, vasodilatory, and anti-inflammatory responses and in lowering blood pressure in various animal models under normal and pathological conditions such as salt-sensitive hypertension, obesity, and diabetes. The scope of this review is to discuss co-localization and heterodimerization as potential molecular mechanisms of AT2R- and MasR-mediated functions including antihypertensive activities. RECENT FINDINGS: Accumulating evidences show that AT2R and MasR are co-localized, make a heterodimer, and are functionally interdependent in producing their physiological responses. Moreover, ang-(1-7) preferably may be an AT1R-biased agonist while acting as a MasR agonist. The physical interactions of AT2R and MasR appear to be an important mechanism by which these receptors are involved in blood pressure regulation and antihypertensive activity. Whether heteromers of these receptors influence affinity or efficacy of endogenous or synthetic agonists remains a question to be considered.
PURPOSE OF REVIEW: Angiotensin type 2 receptor (AT2R) and receptor Mas (MasR) are part of the "protective arm" of the renin angiotensin system. Gene and pharmacological manipulation studies reveal that AT2R and MasR are involved in natriuretic, vasodilatory, and anti-inflammatory responses and in lowering blood pressure in various animal models under normal and pathological conditions such as salt-sensitive hypertension, obesity, and diabetes. The scope of this review is to discuss co-localization and heterodimerization as potential molecular mechanisms of AT2R- and MasR-mediated functions including antihypertensive activities. RECENT FINDINGS: Accumulating evidences show that AT2R and MasR are co-localized, make a heterodimer, and are functionally interdependent in producing their physiological responses. Moreover, ang-(1-7) preferably may be an AT1R-biased agonist while acting as a MasR agonist. The physical interactions of AT2R and MasR appear to be an important mechanism by which these receptors are involved in blood pressure regulation and antihypertensive activity. Whether heteromers of these receptors influence affinity or efficacy of endogenous or synthetic agonists remains a question to be considered.
Entities:
Keywords:
Angiotensin II type 1 receptor; Angiotensin II type 2 receptor; Blood pressure; Dimerization; Functional interdependence; Mas receptor
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