Vendrell M, Pujol M J, Tusell J M, Serratosa J
Department of Pharmacology and Toxicology, C.I.D.-C.S.I.C., Barcelona, Spain.
Brain Res Mol Brain Res. 1992 Aug;14(4):285-92. doi: 10.1016/0169-328x(92)90095-s.
In the present study, a relationship between convulsant activity and two cellular events, changes in calmodulin (CaM) concentration and proto-oncogene c-fos expression has been considered. c-fos has been found activated after the administration of the organochlorine insecticide lindane, the Ca2+ channel agonist Bay K, and N-methyl-D-aspartate (NMDA). The administration of the voltage-dependent Ca2+ channel antagonist nifedipine was able to block the expression elicited by lindane. The effect of lindane on c-fos expression could not be blocked by prior administration of MK-801, a non-competitive antagonist of the NMDA receptor. These results suggest a possible role for the voltage-dependent Ca2+ channels in the mechanism of action of lindane. By means of in situ hybridization, the different patterns of c-fos expression after the administration of the mentioned compounds have been described. A possible modification of the levels of CaM has also been investigated. Among all the subcellular fractions considered, only levels of nuclear CaM appeared to be affected after the different treatments. The changes observed seemed to follow a similar pattern to that described for c-fos induction. Calcium entry through these voltage-dependent calcium channels would be the link between membrane depolarizing events and expression of c-fos and/or increase in nuclear CaM.
在本研究中，已经考虑了惊厥活性与两个细胞事件之间的关系，即钙调蛋白（CaM）浓度的变化和原癌基因c-fos的表达。已发现有机氯杀虫剂林丹、Ca2+通道激动剂Bay K和N-甲基-D-天冬氨酸（NMDA）给药后c-fos被激活。电压依赖性Ca2+通道拮抗剂硝苯地平的给药能够阻断林丹引起的表达。林丹对c-fos表达的影响不能被NMDA受体的非竞争性拮抗剂MK-801预先给药所阻断。这些结果表明电压依赖性Ca2+通道在林丹作用机制中可能起作用。通过原位杂交，已经描述了上述化合物给药后c-fos表达的不同模式。还研究了CaM水平的可能改变。在所有考虑的亚细胞组分中，不同处理后似乎只有核CaM水平受到影响。观察到的变化似乎遵循与c-fos诱导所描述的相似模式。通过这些电压依赖性钙通道的钙内流将是膜去极化事件与c-fos表达和/或核CaM增加之间的联系。
