Cross talk between angiotensin II type 1 and type 2 receptors: Cellular mechanism of angiotensin type 2 receptor-mediated cell growth inhibition

Angiotensin (Ang) II plays an important role in regulating cardiovascular hemodynamics as well as cardiovascular structure. At least two distinct receptor subtypes of Ang II have been defined on the basis of their differential pharmacological and biochemical properties, and designated as Ang II type 1 (AT1) receptor and type 2 (AT2) receptor. Most of the known effects of Ang II in adult tissues are attributable to the AT1 receptor. Recent cloning of the AT2 receptor has revealed a variety of new physiological effects of Ang II. AT1 and AT2 receptors belong to the seven-transmembrane receptor family. However, the function and signaling mechanism of these receptor subtypes are quite different, These receptors seem to exert opposite effects in terms of cardiovascular hemodynamics and cell growth. Growth inhibitory effects of AT2 receptors are unique in that this receptor activates a variety of phosphatases and cross talks with the signaling of other seven-transmembrane, G protein-coupled receptors, as well as other classes of growth factor receptors. We will review recent concepts of the molecular and cellular mechanisms of AT2 receptor action in this article.