Wang J, Cheng J, Chan R, Tseng L, Chou K, Tang K, Chung Lee K, Lo Y, Wang J, Jan C
Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Rd., 813, Kaohsiung, Taiwan.
Toxicol Lett. 2001 Mar 8;119(3):227-33. doi: 10.1016/s0378-4274(01)00262-4.
The effect of fendiline, an anti-anginal drug, on cytosolic free Ca(2+) levels (Ca(2+)) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca(2+) indicator. Fendiline at concentrations between 1 and 200 microM increased Ca(2+) in a concentration-dependent manner and the signal saturated at 100 microM. The Ca(2+) signal was inhibited by 65+/-5% by Ca(2+) removal and by 38+/-5% by 10 microM nifedipine, but was unchanged by 10 microM La(3+) or verapamil. In Ca(2+)-free medium, pre-treatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) store inhibited fendiline-induced intracellular Ca(2+) release. The Ca(2+) release induced by 50 microM fendiline appeared to be independent of IP(3) because the Ca(2+) increase was unaltered by inhibiting phospholipase C with 2 microM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in Ca(2+) by inducing Ca(2+) influx and Ca(2+) release in an IP(3)-independent manner.
以fura-2作为钙离子指示剂，研究了抗心绞痛药物芬地林对MG63人骨肉瘤细胞胞质游离钙离子水平（[Ca(2+)]i）的影响。浓度在1至200微摩尔之间的芬地林以浓度依赖的方式增加[Ca(2+)]i，且在100微摩尔时信号达到饱和。去除钙离子可使钙离子信号抑制65±5%，10微摩尔硝苯地平可使其抑制38±5%，但10微摩尔镧离子（La(3+)）或维拉帕米对其无影响。在无钙培养基中，用1微摩尔毒胡萝卜素（一种内质网钙离子泵抑制剂）预处理以耗尽内质网钙离子储存，可抑制芬地林诱导的细胞内钙离子释放。50微摩尔芬地林诱导的钙离子释放似乎与肌醇三磷酸（IP(3)）无关，因为用2微摩尔U73122抑制磷脂酶C时，[Ca(2+)]i的增加未发生改变。总体而言，结果表明在MG63细胞中，芬地林通过以IP(3)非依赖的方式诱导钙离子内流和钙离子释放，导致[Ca(2+)]i增加。
