Regulated expression of angiotensin II (AT2) binding sites in R3T3 cells.
R3T3 cells are a fibroblast cell line found to selectively express the AT2 subtype of angiotensin II binding sites. We have previously shown that in these cells, the AT2 sites do not appear to be coupled to G-proteins, do not modulate any of the common second messenger pathways associated with activation of angiotensin II receptors, and do not internalize bound ligand. Here we report that expression of AT2 sites in these cells are subject to modulation by a variety of conditions. In actively growing cells the expression of AT2 sites is very low, while in confluent, quiescent cells, the expression of AT2 sites is markedly increased. Addition of serum, or growth factors, to quiescent cells causes a rapid decrease in the number of cell-surface AT2 sites. Further, incubation of cells with ligands that bind to AT2 sites causes a marked increase in the number of these sites in a time and dose dependent manner indicating homologous up-regulation of expression. These results indicate that expression of AT2 sites in R3T3 cells is under sensitive and rapid control and further indicate that these cells may be an excellent model for studying the physiological regulation of expression of these sites.
Dudley
D T
DT
Department of Signal Transduction, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Summerfelt
R M
RM
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D016475:3T3 Cells; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002455:Cell Division; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D008934:Mitogens; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; C073402:PD 123319; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D012504:Saralasin; D019808:Losartan; D001839:Bombesin