gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

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The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II AT1 receptor

Der G-Protein gekoppelte Rezeptor Mas ist ein physiologischer Antagonist des Angiotensin AT1-Rezeptors

Meeting Abstract (Hypertonie 2003)

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  • presenting/speaker T. Walther
  • G. Milligan
  • A. Christopoulos
  • C. Sanchez-Ferrer - Universidad Autónoma, TM7, Madrid
  • S. Heringer-Walther
  • P. Sexton
  • H. Schultheiss
  • E. Kostenis

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP39

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch139.shtml

Published: November 11, 2004

© 2004 Walther et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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The Mas proto-oncogene encodes a G protein-coupled receptor suggested to be involved in the actions of angiotensins. In transfected mammalian cells Mas was not activated by angiotensin II. However, AT1 receptor-mediated, angiotensin II-induced, mobilization of intracellular Ca2+ was diminished by 50% following co-expression 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 two 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-oligomerise with the AT1 receptor and by so doing inhibit the actions of angiotensin II. This is the first 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 interventions in cardiovascular diseases.