Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Pathogenetic Veterinary Science, United Graduate School of Veterinary Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Environ Toxicol Pharmacol. 2009 Jul;28(1):70-7. doi: 10.1016/j.etap.2009.02.006. Epub 2009 Feb 27.
The effects of tributyltin (TBT) on cytosolic Ca(2+) concentration (Ca(2+)) and cell viability were investigated in nerve growth factor-differentiated PC12 cells. TBT concentration dependently increased Ca(2+) with an EC(50) value of 0.07μM. This effect was markedly reduced by removal of the extracellular Ca(2+) or membrane depolarization with a high K(+) medium, but unaffected by thapsigargin causing depletion of intracellular Ca(2+) stores. The L-type voltage-dependent Ca(2+) channel (VDCC) blocker nicardipine blocked the effect of TBT, but the N-type VDCC blocker ω-conotoxin did not. TBT decreased the number of viable cells with an EC(50) value of 0.09μM. The TBT-induced cell death was prevented by nicardipine or by chelating the cytosolic Ca(2+) with BAPTA-AM, but not by ω-conotoxin. The results show that TBT causes an increase in Ca(2+) via activating L-type VDCCs, and support the idea that the organotin-induced cell death arises through Ca(2+) mobilization via L-type VDCCs.
三丁基锡（TBT）对神经生长因子分化的 PC12 细胞胞浆游离钙浓度(Ca(2+))和细胞活力的影响进行了研究。TBT 浓度依赖性地增加Ca(2+)，EC(50)值为 0.07μM。去除细胞外 Ca(2+)或用高 K(+)介质去极化可显著降低这种作用，但不影响 thapsigargin 引起的细胞内 Ca(2+)储存耗竭。L 型电压依赖性钙通道（VDCC）阻滞剂尼卡地平可阻断 TBT 的作用，但 N 型 VDCC 阻滞剂ω-芋螺毒素则无此作用。TBT 以 0.09μM 的 EC(50)值降低了存活细胞的数量。尼卡地平或用 BAPTA-AM 螯合胞浆游离钙可防止 TBT 诱导的细胞死亡，但 ω-芋螺毒素则无此作用。结果表明，TBT 通过激活 L 型 VDCC 引起Ca(2+)增加，并支持有机锡诱导的细胞死亡是通过 L 型 VDCC 引起 Ca(2+)动员的观点。
