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Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas

Item Type:Article
Title:Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas
Creators Name:Santos, R.A.S., e Silva, A.C.S., Maric, C., Silva, D.M.R., Machado, R.P., de Buhr, I., Heringer-Walther, S., Pinheiro, S.V.B., Lopes, M.T., Bader, M., Mendes, E.P., Lemos, V.S., Campagnole-Santos, M.J., Schultheiss, H.P., Speth, R. and Walther, T.
Abstract:The renin-angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. Besides angiotensin (Ang) II, other Ang peptides, such as Ang III [Ang-(2-8)], Ang IV [Ang-(3-8)], and Ang-(1-7) may also have important biological activities. Ang-(1-7) has become an angiotensin of interest in the past few years, because its cardiovascular and baroreflex actions counteract those of Ang II. Unique angiotensin-binding sites specific for this heptapeptide and studies with a selective Ang-(1-7) antagonist indicated the existence of a distinct Ang-(1-7) receptor. We demonstrate that genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene abolishes the binding of Ang-(1-7) to mouse kidneys. Accordingly, Mas-deficient mice completely lack the antidiuretic action of Ang-(1-7) after an acute water load. Ang-(1-7) binds to Mas-transfected cells and elicits arachidonic acid release. Furthermore, Mas-deficient aortas lose their Ang-(1-7)-induced relaxation response. Collectively, these findings identify Mas as a functional receptor for Ang-(1-7) and provide a clear molecular basis for the physiological actions of this biologically active peptide.
Keywords:Binding, Mas Protooncogene, Renin Angiotensin System, Animals, Cricetinae, Cricetulus, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences
Volume:100
Number:14
Page Range:8258-8263
Date:8 July 2003
Official Publication:https://doi.org/10.1073/pnas.1432869100
PubMed:View item in PubMed

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