Molecular biology and signaling of angiotensin receptors: An overview

The well known diversity of angiotensin II (AngII) action is due to the div ersity of its receptors and subsequent intracellular signaling initiated by them. Both type 1 and 2 receptors (AT(1) and AT(2)) were expression-cloned from various species. AT(1) was shown to consist of two isoforms (AT(1A) a nd AT(1B)) in rodents, whereas only one AT(1) was found in higher mammals. Most of the functions hitherto identified with AngII were due to AT(1), but diverse functions are also being identified with AT(2). Although AT(1) and AT(2) are both G protein-coupled receptors, their signals seem to result i n opposite effects. For example, AT(1) causes vascular growth by activating epidermal growth factor receptors and other tyrosine kinase systems, where as AT(2) seems to activate dephosphorylating enzymes, which in extreme situ ations lead to apoptosis. Results of studies with AT(1A) null mice or AT(A) X AT(1B) dual null mice and AT(2)-deleted animals indicate that AT(2) work s in the direction of vasorelaxation as opposed to vasoconstriction by AT(1 ). Although AT(1) works mainly through Gq/11 proteins, it has been shown th at AT(2) binds Gi alpha 2 and Gi alpha 3. However, the exact mechanisms of these actions are not clear and much work is required in many areas.