[Verapamil inhibits the in vitro synthesis of DNA. I. Study of human lymphocyte cultures].
Verapamil in vitro reduced 3H-TdR incorporation into lymphocytes. High doses of Verapamil were lethal for cells; low doses inhibit DNA synthesis, but cell viability by the Trypan blue exclusion method is preserved. Increasing the concentration of Ca++ in the medium partially improved lymphocyte viability and 3H-TdR incorporation. Modification of the Na+ and K+ content in the medium did not interfere with Verapamil action. The inhibitory action was not completely reversible even when the cells were exposed to the drug for a short time (15'). Our results confirm the dependency of lymphocyte blast transformation on Ca++ during the first 20 h. Nifedipine did not inhibit cell replication, which suggests a different mechanism of action. Our investigation suggests that there is more than one model for calcium-antagonism and that the action of Verapamil can not be explained only by its influence on transmembrane Ca++ flux. We believe that Verapamil has a negative action on cell metabolism directly through an interaction on transmembrane Ca++ flux and on intracellular Ca++.
D002118:Calcium / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology* / Q000633:toxicity
D004247:DNA; D014700:Verapamil; D002118:Calcium
Il Verapamil inibisce la sintesi del DNA "in vitro". I. Studio su colture di linfociti umani.