Cesano L, Vietti Ramus G, Tartaglino B, Barbalonga A
Minerva Med. 1985 Sep 15;76(34-35):1541-8.
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++.
维拉帕米在体外可减少3H-胸苷掺入淋巴细胞。高剂量的维拉帕米对细胞具有致死性；低剂量则抑制DNA合成，但通过台盼蓝排斥法检测细胞活力得以保留。增加培养基中Ca++的浓度可部分改善淋巴细胞活力及3H-胸苷掺入情况。改变培养基中Na+和K+的含量并不干扰维拉帕米的作用。即使细胞短时间（15分钟）暴露于该药物，其抑制作用也并非完全可逆。我们的结果证实了在最初20小时内淋巴细胞增殖转化对Ca++的依赖性。硝苯地平并不抑制细胞复制，这提示了其不同的作用机制。我们的研究表明，钙拮抗作用存在不止一种模式，且维拉帕米的作用不能仅通过其对跨膜Ca++通量的影响来解释。我们认为，维拉帕米通过与跨膜Ca++通量及细胞内Ca++相互作用，直接对细胞代谢产生负面作用。
