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

作者：Robson A.S. Santos, Ana Cristina Simões e Silva, Christine Maric, Denise M. R. Silva, R.P. Machado, Insa de Buhr, Silvia Heringer‐Walther, Sérgio Veloso Brant Pinheiro, Myriam Teresa Lopes, Michael Bäder, Elizabeth Pereira Mendes, Virginia Soares Lemos, Maria José Campagnole‐Santos, Heinz‐Peter Schultheiss, Robert Charles Speth, Thomas Walther · 发表于：Proceedings of the National Academy of Sciences · 年份：2003 · DOI：10.1073/pnas.1432869100 · 被引用次数：1818 · 研究领域：Renin-Angiotensin System Studies、Receptor Mechanisms and Signaling、Neuropeptides and Animal Physiology

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.