Effect of different convulsants on calmodulin levels and proto-oncogene c-fos expression in the central nervous system.
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.
Vendrell
M
M
Department of Pharmacology and Toxicology, C.I.D.-C.S.I.C., Barcelona, Spain.
Pujol
M J
MJ
Tusell
J M
JM
Serratosa
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002147:Calmodulin / Q000378:metabolism*; D002467:Cell Nucleus / Q000648:ultrastructure; D003292:Convulsants / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013574:Synaptosomes / Q000648:ultrastructure
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002147:Calmodulin; D003292:Convulsants; D009419:Nerve Tissue Proteins; D001556:Hexachlorocyclohexane