Publikationsdatenbank

G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor (2005)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Kostenis, Evi

Milligan, Graeme

Christopoulos, Arthur

Sanchez-Ferrer, Carlos F

Heringer-Walther, Silvia

Sexton, Patrick M

Gembardt, Florian

Kellett, Elaine

Martini, Lene

Vanderheyden, Patrick

Schultheiss, Heinz-Peter

Walther, Thomas

Quelle

Circulation

Bandzählung: 111

Heftzählung: 14

Seiten: 1806 – 1813

ISSN: 0009-7322

Sprache

Englisch

Verweise

Pubmed: 15809376

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

We previously identified the G-protein-coupled receptor Mas, encoded by the Mas proto-oncogene, as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. We therefore tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT1.

In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT1 receptor-mediated, angiotensin II-induced production of inositol phosphates and mobilization of intracellular Ca2+ was diminished by 50% after coexpression of Mas, despite a concomitant increase in angiotensin II binding capacity. Mas and the AT1 receptor formed a constitutive hetero-oligomeric complex that was unaffected by the presence of agonists or antagonists of the 2 receptors. In vivo, Mas acts as an antagonist of the AT1 receptor; mice lacking the Mas gene show enhanced angiotensin II-mediated vasoconstriction in mesenteric microvessels.

These results demonstrate that Mas can hetero-oligomerize with the AT1 receptor and by so doing inhibit the actions of angiotensin II. This is a novel demonstration that a G-protein-coupled receptor acts as a physiological antagonist of a previously characterized receptor. Consequently, the AT1-Mas complex could be of great importance as a target for pharmacological intervention in cardiovascular diseases.