Molecular biology and signaling of angiotensin receptors: an overview.

The well known diversity of angiotensin II (AngII) action is due to the diversity of its receptors and subsequent intracellular signaling initiated by them. Both type 1 and 2 receptors (AT1 and AT2) were expression-cloned from various species. AT1 was shown to consist of two isoforms (AT1A and AT1B) in rodents, whereas only one AT1 was found in higher mammals. Most of the functions hitherto identified with AngII were due to AT1, but diverse functions are also being identified with AT2. Although AT1 and AT2 are both G protein-coupled receptors, their signals seem to result in opposite effects. For example, AT1 causes vascular growth by activating epidermal growth factor receptors and other tyrosine kinase systems, whereas AT2 seems to activate dephosphorylating enzymes, which in extreme situations lead to apoptosis. Results of studies with AT1A null mice or ATA X AT1B dual null mice and AT2-deleted animals indicate that AT2 works in the direction of vasorelaxation as opposed to vasoconstriction by AT1. Although AT1 works mainly through Gq/11 proteins, it has been shown that AT2 binds Gialpha2 and Gialpha3. However, the exact mechanisms of these actions are not clear and much work is required in many areas.