Artikel
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
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Autoren
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T. Walther
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G. Milligan
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A. Christopoulos
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C. Sanchez-Ferrer
- Universidad Autónoma, TM7, Madrid
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S. Heringer-Walther
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P. Sexton
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H. Schultheiss
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E. Kostenis
| Veröffentlicht: | 11. November 2004 |
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Gliederung
Text
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.
