New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D.
The renin-angiotensin system is an important component of the central and humoral mechanisms of blood pressure and hydro-electrolytic balance control. Angiotensin II is a key player of this system. Twenty-five years ago the first manuscripts describing the formation and actions of another peptide of the RAS, angiotensin-(1-7), were published. Since then several publications have shown that angiotensin-(1-7) is as pleiotropic as angiotensin II, influencing the functions of many organs and systems. The identification of the ACE homologue ACE2 and, a few years later, Mas, as a receptor for angiotensin-(1-7) contributed a great deal to establish this peptide as a key player of the RAS. Most of the actions of angiotensin-(1-7) are opposite to those described for angiotensin II. This has led to the concept of two arms of the RAS: one comprising ACE/AngII/AT1R and the other ACE2/Ang-(1-7)/Mas. More recently, we have described the identification of a novel component of the RAS, alamandine, which binds to the Mas-related G protein coupled receptor D. This peptide is formed by decarboxylation of the Asp residue of angiotensin-(1-7), leading to the formation of Ala as the N-terminal amino acid. Alternatively, it can be formed by hydrolysis of Ang A, by ACE2. Its effects include vasorelaxation, central effects similar to those produced by angiotensin-(1-7), blunting of isoproterenol-induced heart fibrosis, and anti-hypertensive action in SHR. The putative enzyme responsible for alamandine formation from angiotensin-(1-7) is under investigation. The identification of this novel component of the RAS opens new venues for understanding its physiological role and opens new putative therapeutic possibilities for treating cardiovascular diseases.
National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Federal University of Minas Gerais, Av. Antonio Carlos, 6627 - ICB - UFMG, 31270-901, Belo Horizonte, MG, Brazil.
Gisele Maia
GM
Etelvino
Antônio Augusto Bastos
AA
Peluso
Robson Augusto Souza
RA
Santos
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D000959:Antihypertensive Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C581752:alamandine; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)