Regulation of c-fos expression by convulsants and hexachlorocyclohexane isomers in primary cultures of cortical neurons.
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.
Barrón
S
S
Department of Pharmacology and Toxicology, CID-CSIC, Barcelona, Spain.
Serratosa
J
J
Tusell
J M
JM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007536:Isomerism; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003292:Convulsants; D016760:Proto-Oncogene Proteins c-fos; D001556:Hexachlorocyclohexane; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester