The Angiotensin II AT2 Receptor Is an AT1 Receptor Antagonist

The vasopressor angiotensin II activates AT1 and AT2 receptors. Most of the known in 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 AT2 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.