Item Type: | Article |
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Title: | Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas |
Creators Name: | Santos, R.A.S. and e Silva, A.C.S. and Maric, C. and Silva, D.M.R. and Machado, R.P. and de Buhr, I. and Heringer-Walther, S. and Pinheiro, S.V.B. and Lopes, M.T. and Bader, M. and Mendes, E.P. and Lemos, V.S. and Campagnole-Santos, M.J. and Schultheiss, H.P. and 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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