Barrón S, Serratosa J, Tusell J M
Department of Pharmacology and Toxicology, CID-CSIC, Barcelona, Spain.
J Neurochem. 1995 Apr;64(4):1708-14. doi: 10.1046/j.1471-4159.1995.64041708.x.
Primary cortical cultures were used to study the effects of four convulsants on c-fos expression. Approximately 30% of the neurons in these cultures displayed c-fos nuclear immunostaining under basal conditions. The addition of tetrodotoxin, nifedipine, or delta-hexachlorocyclohexane produced a significant decrease in c-fos basal values. Lindane (gamma-hexachlorocyclohexane), Bay K 8644, pentylenetetrazole, and picrotoxinin produced a significant increase in c-fos immunoreactivity and in c-fos mRNA expression. Treatment of cells with tetrodotoxin before administration of the convulsant agents lowered c-fos staining below basal levels. In contrast, delta-hexachlorocyclohexane or nifedipine failed to block only the picrotoxin-induced increase. The differential pattern of expression shown by c-fos after these treatments suggests various mechanisms of action for the compounds studied. The results obtained with delta-hexachlorocyclohexane and nifedipine suggest that picrotoxinin activates c-fos expression by calcium-requiring intracellular signaling pathways that are different from those activated by Bay K 8644, pentylenetetrazole, or gamma-hexachlorocyclohexane, which, at least in part, act via L-type calcium channels.
原代皮层培养物被用于研究四种惊厥剂对c-fos表达的影响。在基础条件下，这些培养物中约30%的神经元显示出c-fos核免疫染色。添加河豚毒素、硝苯地平或δ-六六六导致c-fos基础值显著降低。林丹（γ-六六六）、Bay K 8644、戊四氮和印防己毒素导致c-fos免疫反应性和c-fos mRNA表达显著增加。在给予惊厥剂之前用河豚毒素处理细胞，使c-fos染色低于基础水平。相比之下，δ-六六六或硝苯地平仅未能阻断印防己毒素诱导的增加。这些处理后c-fos显示的差异表达模式表明所研究化合物的各种作用机制。用δ-六六六和硝苯地平获得的结果表明，印防己毒素通过需要钙的细胞内信号通路激活c-fos表达，这些信号通路不同于Bay K 8644、戊四氮或γ-六六六激活的信号通路，后者至少部分通过L型钙通道起作用。
