Oyama Y, Chikahisa L, Hayashi A, Ueha T, Sato M, Matoba H
Department of Health Sciences, Faculty of Integrated Arts and Sciences, University of Tokushima, Japan.
Jpn J Pharmacol. 1992 Apr;58(4):467-71. doi: 10.1254/jjp.58.467.
To test the possibility that triphenyltin (TPT) increases the intracellular Ca2+ ([Ca2+]i) in neurons as found previously in thymocytes, the effect of TPT on [Ca2+]i was examined in rat cerebellar neurons by a flow-cytometer with fluorescent dyes. TPT at concentrations ranging from 3 x 10(-7) M to 1 x 10(-5) M dose-dependently increased the [Ca2+]i. The TPT-induced increase in [Ca2+]i was not attenuated by a Ca2+ channel blocker, suggesting that it was not dependent on voltage-dependent Ca2+ channels. As the concentration of external Ca2+ ([Ca2+]e) increased, TPT produced a more profound increase in the [Ca2+]i. However, the increase in the [Ca2+]i by TPT was observed even in nominally [Ca2+]e-free solution. These results suggest two possibilities. First, TPT may promote Ca(2+)-influx to the neuron. Secondly, TPT may affect the intracellular Ca-store sites. This study is relevant to the neurotoxicity of organotins because it has become progressively clear that sustained increases in the [Ca2+]i can activate various Ca(2+)-dependent degradative processes.
为了验证三苯基锡（TPT）是否如先前在胸腺细胞中所发现的那样增加神经元内的钙离子浓度（[Ca2+]i），我们通过使用荧光染料的流式细胞仪检测了TPT对大鼠小脑神经元[Ca2+]i的影响。浓度范围为3×10（-7）M至1×10（-5）M的TPT呈剂量依赖性地增加[Ca2+]i。TPT诱导的[Ca2+]i增加并未被钙离子通道阻滞剂减弱，这表明其不依赖于电压依赖性钙离子通道。随着细胞外钙离子浓度（[Ca2+]e）的增加，TPT使[Ca2+]i产生更显著的增加。然而，即使在名义上无[Ca2+]e的溶液中，也观察到TPT使[Ca2+]i增加。这些结果提示了两种可能性。第一，TPT可能促进钙离子流入神经元。第二，TPT可能影响细胞内钙离子储存位点。这项研究与有机锡的神经毒性相关，因为越来越清楚的是，[Ca2+]i的持续增加可激活各种钙离子依赖性降解过程。
