Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas
Proceedings of the National Academy of Sciences (PNAS)
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.
Santos, Robson A.; Simoes e Silva, Ana C.; Maric, Christine; Silva, Denise M.; Machado, Raquel Pillar; de Buhr, Insa; Heringer-Walther, Silvia; Pinheiro, Sergio Veloso; Lopes, Myriam Teresa; Bader, Michael; Mendes, Elizabeth P.; Lemos, Virgina Soares; Campagnole-Santos, Maria Jose; Schultheiss, Heinz-Peter; Speth, Robert; and Walther, Thomas, "Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas" (2003). HPD Articles. 120.