The angiotensin II type 2 receptor primarily inhibits cell growth via pertussis toxin-sensitive G proteins.

We examined the effects of angiotensin II (Ang II) and its analogue CGP42112 on cell growth through the Ang II type 2 receptor (AT2) and the involvement of pertussis toxin (PTX)-sensitive G proteins in the AT2-mediated pathway. Both Ang II and CGP42112 inhibited DNA synthesis in serum-stimulated NIH3T3 fibroblast cells stably expressing recombinant AT2 in a dose-dependent manner with almost the same potency. This effect was abolished by the AT2-selective antagonist PD123319, but not by the Ang II type 1 receptor-specific antagonist DuP753, suggesting that AT2 mediates the event. The anti-proliferative effect was also blocked by PTX treatment. Together, these data suggest that CGP42112 as well as Ang II primarily has an AT2-mediated inhibitory activity on serum-stimulated cell growth, and PTX-sensitive G proteins are essential in this AT2-induced event.