Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas.
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 S
RA
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, 31270, Minas Gerais, Brazil.
Simoes e Silva
Ana C
AC
Maric
Christine
C
Silva
Denise M R
DM
Machado
Raquel Pillar
RP
de Buhr
Insa
I
Heringer-Walther
Silvia
S
Pinheiro
Sergio Veloso B
SV
Lopes
Myriam Teresa
MT
Bader
Michael
M
Mendes
Elizabeth P
EP
Lemos
Virgina Soares
VS
Campagnole-Santos
Maria Jose
MJ
Schultheiss
Heinz-Peter
HP
Speth
Robert
R
Walther
Thomas
T
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
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)