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

Authors

Robson A. Santos, Federal University of Minas Gerais
Ana C. Simoes e Silva, Federal University of Minas Gerais
Christine Maric, Georgetown University
Denise M. Silva, Federal University of Minas Gerais
Raquel Pillar Machado, Federal University of Minas Gerais
Insa de Buhr, Free University
Silvia Heringer-Walther, Free University
Sergio Veloso Pinheiro, Federal University of Minas Gerais
Myriam Teresa Lopes, Federal University of Minas Gerais
Michael Bader, Max Delbruck Center
Elizabeth P. Mendes, Federal University of Minas Gerais
Virgina Soares Lemos, Federal University of Minas Gerais
Maria Jose Campagnole-Santos, Federal University of Minas Gerais
Heinz-Peter Schultheiss, Free University
Robert Speth, Washington State UniversityFollow
Thomas Walther, Georgetown University

Document Type

Article

Publication Date

7-8-2003

Publication Title

Proceedings of the National Academy of Sciences (PNAS)

ISSN

0027-8424

Volume

100

Issue/No.

14

First Page

8258

Last Page

63

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.

NSUWorks Citation

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.
https://nsuworks.nova.edu/hpd_facarticles/120

ORCID ID

0000-0002-6434-2206

DOI

10.1073/pnas.1432869100