title: Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas.
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.
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, 31270, Minas Gerais, Brazil.
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.forename: Ana C
authors.initials: AC
authors.lastname: Simoes e Silva
authors.forename: Christine
authors.initials: C
authors.lastname: Maric
authors.forename: Denise M R
authors.initials: DM
authors.lastname: Silva
authors.forename: Raquel Pillar
authors.initials: RP
authors.lastname: Machado
authors.forename: Insa
authors.initials: I
authors.lastname: de Buhr
authors.forename: Silvia
authors.initials: S
authors.lastname: Heringer-Walther
authors.forename: Sergio Veloso B
authors.initials: SV
authors.lastname: Pinheiro
authors.forename: Myriam Teresa
authors.initials: MT
authors.lastname: Lopes
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Mendes
authors.forename: Virgina Soares
authors.initials: VS
authors.lastname: Lemos
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Campagnole-Santos
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Robert
authors.initials: R
authors.lastname: Speth
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004231:Diuresis / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008024:Ligands; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D016718:Arachidonic Acid; D000803:Angiotensin I; C118790:angiotensin I (1-7)