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

被引:1385
作者
Santos, RAS
Silva, ACSE
Maric, C
Silva, DMR
Machado, RP
de Buhr, I
Heringer-Walther, S
Pinheiro, SVB
Lopes, MT
Bader, M
Mendes, EP
Lemos, VS
Campagnole-Santos, MJ
Schultheiss, HP
Speth, R
Walther, T
机构
[1] Free Univ Berlin, Univ Hosp Benjamin Franklin, Dept Cardiol & Pneumol, D-12200 Berlin, Germany
[2] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
[3] Washington State Univ, Dept Vet & Comparat Anat Pharmacol & Physiol, Pullman, WA 99164 USA
[4] Georgetown Univ, Dept Med, Washington, DC 20057 USA
[5] Univ Fed Minas Gerais, Dept Physiol & Biophys, BR-31270 Belo Horizonte, MG, Brazil
关键词
binding; Mas protooncogene; renin angiotensin system;
D O I
10.1073/pnas.1432869100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8258 / 8263
页数:6
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