The AT(2) receptor selectively associates with G(i alpha 2) and G(i alpha 3) in the rat fetus

The effects of angiotensin II are mediated by a family of seven transmembrane receptors. In the adult, the majority of the receptors are of the AT(1) isoform, which is coupled to heterotrimeric G proteins (either G(q alpha) or G(i alpha)). In contrast, the AT(2) receptor is expressed at low levels in the adult but is the major form expressed in the fetal and neonatal animal. Previous results have failed to show G protein coupling of the AT(2) receptor in the fetus. We now provide evidence that the AT(2) receptor is G protein-coupled. An antibody that binds several G(alpha) subunits immunoselected angiotensin II receptor-G(alpha) complexes. In addition, G(i alpha 1-3) antibody, which recognizes G(i alpha 1), G(i alpha 2) and G(i alpha 3), also co-immunoselect the AT(2) recep tor. Anti-G(i alpha 2) and anti-G(i alpha 3) antibodies were both able to co-immunoselected AT(2) receptor-G(i alpha) complexes, but consistent with the lack of G(i alpha 1) in the fetal extracts, anti-G(i alpha 1), antibodies did not nor did any other G protein-directed antisera. The finding that AT(2) receptor couples to both G(i alpha 2) and G(i alpha 3) raises the possibility that selective interactions between AT(2) receptor and different G proteins may result in specific cellular effects mediated by AT(2) stimulation.