Calcium influx modulates DNA synthesis and proliferation in A7r5 vascular smooth muscle cells.
In A7r5 vascular smooth muscle cultures basal Ca2+ influx was higher in growing versus quiescent cells (P less than 0.05), due primarily to a five-fold increase in dihydropyridine-inhibitable Ca2+ influx (P less than 0.005). Verapamil decreased [3H]thymidine incorporation in a concentration dependent fashion with a significant 6 +/- 2% inhibition at 0.1 microM and a maximal inhibition of 67 +/- 2% at 100 microM. Similarly, nitrendipine inhibited fetal calf serum-stimulated [3H]thymidine incorporation with a threshold concentration of 1 nM and a maximal inhibition of 79 +/- 12% at 10 microM. In quiescent cells, verapamil (10 microM) inhibited the increases in [3H]thymidine incorporation stimulated by fetal calf serum, serotonin, vasopressin or 12-0-tetradecanoyl phorbol-13-acetate by 37-43% (P less than 0.001 vs. control for all). Finally, verapamil (100 microM) and nitrendipine (10 microM) inhibited proliferation by 39 +/- 10 and 20 +/- 6%, respectively (P less than 0.01 and 0.02 vs. control, respectively). Thus in A7r5 cells, proliferation is associated with increased Ca2+ influx via dihydropyridine-sensitive Ca2+ channels and organic Ca2+ channel antagonists inhibit DNA synthesis and cell proliferation.
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
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Colucci
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics / Q000502:physiology; D002132:Calcium Radioisotopes; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014667:Vasopressins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002132:Calcium Radioisotopes; C028521:lanthanum chloride; D014316:Tritium; D014667:Vasopressins; D012701:Serotonin; D004533:Egtazic Acid; D007811:Lanthanum; D004247:DNA; D009568:Nitrendipine; D014700:Verapamil; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine