THE ANGIOTENSIN-II TYPE-2 RECEPTOR PRIMARILY INHIBITS CELL-GROWTH VIAPERTUSSIS-TOXIN-SENSITIVE G-PROTEINS

We examined the effects of angiotensin II (Ang II) and its analogue CG P42112 on cell growth through the Ang II type 2 receptor (AT(2)) and t he involvement of pertussis toxin (PTX)-sensitive G proteins in the AT (2)-mediated pathway. Both Ang II and CGP42112 inhibited DNA synthesis in serum-stimulated NIH3T3 fibroblast cells stably expressing recombi nant AT(2) in a dose-dependent manner with almost the same potency. Th is effect was abolished by the AT(2)-selective antagonist PD123319, bu t net by the Ang II type 1 receptor-specific antagonist DuP753, sugges ting that AT(2) mediates the event. The anti-proliferative effect was also blocked by PTX treatment. Together, these data suggest that CGP42 112 as well as Ang II primarily has an AT(2)-mediated inhibitory activ ity on serum-stimulated cell growth, and PTX-sensitive G proteins are essential in this AT(2)-induced event. (C) 1996 Academic Press, Inc.