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.
Ozawa
Y
Y
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Suzuki
Y
Y
Murakami
K
K
Miyazaki
H
H
D016475:3T3 Cells; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D019808:Losartan; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D011994:Recombinant Proteins; D013777:Tetrazoles; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; C060894:CGP 42112A; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D019808:Losartan