Santos Robson A S, Simoes e Silva Ana C, Maric Christine, Silva Denise M R, Machado Raquel Pillar, de Buhr Insa, Heringer-Walther Silvia, Pinheiro Sergio Veloso B, Lopes Myriam Teresa, Bader Michael, Mendes Elizabeth P, Lemos Virgina Soares, Campagnole-Santos Maria Jose, Schultheiss Heinz-Peter, Speth Robert, Walther Thomas
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, 31270, Minas Gerais, Brazil.
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. doi: 10.1073/pnas.1432869100. Epub 2003 Jun 26.
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.
肾素-血管紧张素系统在血压控制以及体液和电解质平衡方面发挥着关键作用。除了血管紧张素（Ang）II外，其他Ang肽，如Ang III [Ang-(2-8)]、Ang IV [Ang-(3-8)]和Ang-(1-7)也可能具有重要的生物学活性。在过去几年中，Ang-(1-7)已成为一种备受关注的血管紧张素，因为其心血管和压力反射作用可抵消Ang II的作用。针对这种七肽的独特血管紧张素结合位点以及使用选择性Ang-(1-7)拮抗剂的研究表明存在一种独特的Ang-(1-7)受体。我们证明，由Mas原癌基因编码的G蛋白偶联受体的基因缺失消除了Ang-(1-7)与小鼠肾脏的结合。因此，急性水负荷后，Mas基因缺陷小鼠完全缺乏Ang-(1-7)的抗利尿作用。Ang-(1-7)与转染Mas的细胞结合并引发花生四烯酸释放。此外，Mas基因缺陷的主动脉失去了Ang-(1-7)诱导的舒张反应。这些发现共同确定Mas为Ang-(1-7)的功能性受体，并为这种生物活性肽的生理作用提供了明确的分子基础。
