Effects of retinoic acid on alkaline phosphatase messenger ribonucleic acid, catecholamine receptors, and G proteins in ROS 17/2.8 cells.
Retinoic acid (RA) inhibits the increases in alkaline phosphatase (AP) and hormone-stimulated adenylate cyclase that accompany the growth of ROS 17/2.8 osteosarcoma cells in culture. The RA effects were first detected 2 days after initiation of treatment and were dose dependent, with an EC50 of 100 nM. The reduction in the hormone-responsive adenylate cyclase activity was associated with lower levels of beta-catecholamine receptors, without a change in apparent receptor affinity and with lower levels of the GTP-binding proteins Gs and Gi, visualized by NAD-dependent [32P]ADP ribosylation. The reduction in AP was correlated with a decrease in the steady state level of AP mRNA. RA had no effect on cell proliferation or saturation density. Retinoids thus inhibit the same features that are promoted by glucocorticoids in ROS 17/2.8 cells. These features seem to be subject to coordinate regulation, probably at the pretranslational level.
Imai
Y
Y
Department of Bone Biology and Osteoporosis Research, Merck, Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Rodan
S B
SB
Rodan
G A
GA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004167:Diphtheria Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008858:Microscopy, Phase-Contrast; D009243:NAD / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D017983:Receptors, Catecholamine; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004167:Diphtheria Toxin; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D017983:Receptors, Catecholamine; D009243:NAD; D014212:Tretinoin; D020120:Iodocyanopindolol; D002772:Cholera Toxin; D010869:Pindolol; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol