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Volume 271, Number 25, Issue of June 21, 1996 pp. 15026-15033
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

The AT2 Receptor Selectively Associates with Gialpha 2 and Gialpha 3 in the Rat Fetus

(Received for publication, March 7, 1996)

Jisi Zhang and Richard E. Pratt

From the Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California 94305-5246

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 AT1 isoform, which is coupled to heterotrimeric G proteins (either Gqalpha or Gialpha ). In contrast, the AT2 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 AT2 receptor in the fetus. We now provide evidence that the AT2 receptor is G protein-coupled. An antibody that binds several Galpha subunits immunoselected angiotensin II receptor-Galpha complexes. In addition, Gialpha 1-3 antibody, which recognizes Gialpha 1, Gialpha 2 and Gialpha 3, also co-immunoselect the AT2 receptor. Anti-Gialpha 2 and anti-Gialpha 3 antibodies were both able to co-immunoselected AT2 receptor-Gialpha complexes, but consistent with the lack of Gialpha 1 in the fetal extracts, anti-Gialpha 1 antibodies did not nor did any other G protein-directed antisera. The finding that AT2 receptor couples to both Gialpha 2 and Gialpha 3 raises the possibility that selective interactions between AT2 receptor and different G proteins may result in specific cellular effects mediated by AT2 stimulation.


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