The Angiotensin II AT2 Receptor Is an AT1Receptor Antagonist*
- From the ‡Medical Research Center, Ain Shams University Hospital, Cairo, Egypt, the§Heinrich-Pette-Institut, Martinistrasse 52, 20251 Hamburg, Germany, and the ¶Institut für Pharmakologie und Toxikologie, Versbacher Strasse 9, D-97078 Würzburg, Germany
Abstract
The vasopressor angiotensin II activates AT1 and AT2 receptors. Most of the knownin vivo effects of angiotensin II are mediated by AT1 receptors while the biological functions of AT2 receptors are less clear. We report here that the AT2 receptor binds directly to the AT1 receptor and thereby antagonizes the function of the AT1 receptor. The AT1-specific antagonism of the AT2 receptor was independent of AT2 receptor activation and signaling, and it was effective on different cells and on human myometrial biopsies with AT1/AT2 receptor expression. Thus, the AT2 receptor is the first identified example of a G-protein-coupled receptor which acts as a receptor-specific antagonist.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‖ To whom correspondence should be addressed: Insitut für Pharmakologie und Toxikologie, Versbacher Strasse 9, D-97078 Würzburg, Germany. Tel.: 49-931-201-3982; Fax: 49-931-201-3539; E-mail: toph029@rzbox.uni-wuerzburg.de.
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Published, JBC Papers in Press, August 15, 2001, DOI 10.1074/jbc.M105253200
- Abbreviations:
- DST
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disuccinimidyl tartarate
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- Received June 7, 2001.
- Revision received July 23, 2001.
- The American Society for Biochemistry and Molecular Biology, Inc.
