Effect of calcium antagonists on RNA synthesis of NIH 3T3 cells.
Calcium antagonists have been shown to induce a decrease in peripheral vascular resistance as well as a decrease in synthesis of vascular-wall matrix proteins. It has been shown previously that calcium antagonists decrease RNA synthesis of cultured, vascular, smooth-muscle cells. Here, these findings are extended to the investigation of whether calcium antagonists produce their vascular effects through their action on vascular, smooth-muscle cells only or whether they regulate fibroblast cells as well. It is demonstrated that in a concentration-dependent manner verapamil, diltiazem, and nifedipine each induced a decrease in RNA synthesis of quiescent and serum-stimulated NIH 3T3 cells, a fibroblast cell line shown to express voltage-dependent Ca2+ channels. Verapamil and nifedipine (10(-5)M) and diltiazem (10(-4)M) caused a marked decrease of basal and serum-induced increase in [3H]uridine uptake of NIH 3T3 cells. This is the first report to demonstrate that calcium antagonists have a direct effect on a fibroblast cell line leading to a decrease of RNA synthesis. Such findings suggest that calcium-antagonist vascular effects extend beyond vascular smooth muscle cells to connective tissues associated with extracellular-matrix protein production.
Andrawis
N S
NS
Program in Clinical Pharmacology, Brown University School of Medicine, Providence, Rhode Island.
Abernethy
D R
DR
D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003470:Culture Media; D004110:Diltiazem / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis* / Q000187:drug effects; D014529:Uridine / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003470:Culture Media; D012313:RNA; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D014529:Uridine