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

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63. doi: 10.1073/pnas.1432869100. Epub 2003 Jun 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / antagonists & inhibitors
  • Angiotensin I / pharmacology
  • Angiotensin I / physiology*
  • Animals
  • Aorta / drug effects
  • Arachidonic Acid / metabolism
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Diuresis / drug effects
  • Kidney / metabolism*
  • Ligands
  • Mice
  • Mice, Knockout
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • Vasodilation / drug effects

Substances

  • Ligands
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • Arachidonic Acid
  • Angiotensin I
  • angiotensin I (1-7)