Alamandine and Its Receptor MrgD Pair Up to Join the Protective Arm of the Renin-Angiotensin System.

Johanna Schleifenbaum

doi:10.3389/fmed.2019.00107

Abstract

Only a few years ago, alamandine was found to be a member of the protective arm of the renin-angiotensin system. It turned out to be an endogenous ligand of the G protein-coupled receptor MrgD. So far, MrgD had predominantly been studied in a neuronal context. The expression of the receptor in non-neuronal tissue showed hitherto unknown effects mediated by MrgD, most strikingly alamandine-induced vasodilation. Alamandine being a part of the non-classical renin-angiotensin system, a protective role of receptor activation seemed natural. This review summarizes the different effects of MrgD activation by alamandine in vasculature, in the central nervous system, and in organs as kidney and heart. Alamandine and MrgD are promising novel drug targets to protect the kidney and heart through anti-hypertensive actions.

Highlights

When it comes to discussing G protein-coupled receptors (GPCRs) involvement in the development of hypertension, the first molecule that comes into everyone’s mind is usually the angiotensin II receptor
There are only a few studies about the MrgD receptor and its endogenous ligand alamandine, but many of them show a clear relevance of both molecules for the cardiovascular system
Most striking is an increased expression of NOS enzymes upon alamandine-induced activation of MrgD, leading to NO-mediated vasodilation

Summary

INTRODUCTION

When it comes to discussing G protein-coupled receptors (GPCRs) involvement in the development of hypertension, the first molecule that comes into everyone’s mind is usually the angiotensin II receptor. The combination of the search terms “angiotensin receptor” and “hypertension” presents more than 7,000 publications on Pubmed Many of those publications discuss the angiotensin II receptor subtype 1 (AT1R) as the “bad guy” promoting the development of hypertension, inflammation, remodeling, and more. The search term “MrgD” provides only 42 publications in total on Pubmed This can be explained by the fact that the investigation of the MrgD receptor in non-neuronal tissue started only a few years ago. Oliveira et al localized the receptor in blood vessels, cardiomyocytes (mainly in the membrane, perinuclear, and nuclear region), and the cardiovascular center of the mouse brain They studied MrgD-deficient mice and found left ventricular remodeling and a pronounced dilated cardiomyopathy, decreasing the systolic function of the mice (13). The MrgD ligand alamandine was able to attenuate hypertension and alleviate cardiac hypertrophy in this model (14)

G PROTEIN COUPLING

SUMMARY