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 becom...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 14; pp. 8258 - 8263
Main Authors:	Robson A. S. Santos, Ana C. Simoes e Silva, Maric, Christine, Denise M. R. Silva, Machado, Raquel Pillar, de Buhr, Insa, Heringer-Walther, Silvia, Sergio Veloso B. Pinheiro, Lopes, Myriam Teresa, Bader, Michael, Mendes, Elizabeth P., Lemos, Virgina Soares, Campagnole-Santos, Maria Jose, Schultheiss, Heinz-Peter, Speth, Robert, Walther, Thomas
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 08-07-2003 National Acad Sciences
Subjects:	Angiotensin I - antagonists & inhibitors Angiotensin I - pharmacology Angiotensin I - physiology Animals Aorta - drug effects Arachidonic Acid - secretion Biological Sciences Cercopithecus aethiops CHO Cells COS Cells Cricetinae Cricetulus Diuresis Diuresis - drug effects Hypertension Kidney - metabolism Kidneys Ligands Mice Mice, Knockout Neurotransmitters Peptide Fragments - antagonists & inhibitors Peptide Fragments - pharmacology Peptide Fragments - physiology Proteins Proto-Oncogene Proteins - deficiency Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - physiology Receptors Receptors, G-Protein-Coupled Recombinant Fusion Proteins - physiology T tests Transfection Urine Vasodilation - drug effects
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Present address: Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677-1848. This paper was submitted directly (Track II) to the PNAS office. Edited by Richard P. Lifton, Yale University School of Medicine, New Haven, CT Abbreviations: Ang, angiotensin; AVP, arginine-vasopressin; AA, arachidonic acid; CHO, Chinese hamster ovary.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.1432869100