Anticonvulsant activity of calmodulin antagonist W-7 in convulsions induced by lindane and BayK-8644: effects in c-fos expression.
The anticonvulsant activity of calmodulin antagonist W-7, was investigated on convulsions induced in mice by the insecticide lindane and by the calcium channel agonist BayK-8644. We also studied the inhibitory effect of W-7 on on c-fos mRNA expression induced by both convulsants. We observed a good correlation between doses and the acute convulsive effects of lindane and BayK-8644. The incidence rate and time to onset were clearly dose-dependent. W-7 antagonized the convulsive effects of lindane and BayK-8644 in all the parameters studied. A significant decrease in the incidence rate and time to onset were observed when they are compared with the values obtained with the ED100 of lindane- and BayK-8644 induced seizures. Both were able to activate the mRNA expression of the proto-oncogene. The pattern of this expression displayed by in situ hybridization was very similar. A dramatic increase was found in dentate gyrus and high levels of mRNA expression also occurring in hippocampal fields and cortical regions. In accordance with the behavioural results, W-7 antagonized also the c-fos expression induced by lindane and BayK-8644. Our results suggest that lindane as BayK-8644 may activate voltage-dependent calcium channels leading to calmodulin activation.
Tusell
J M
JM
Department of Neurochemistry, C.I.D.-C.S.I.C., Barcelona, Spain.
Barron
S
S
Serratosa
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012640:Seizures / Q000139:chemically induced; D013449:Sulfonamides / Q000494:pharmacology*
D000927:Anticonvulsants; D015220:Calcium Channels; D012333:RNA, Messenger; D013449:Sulfonamides; D001556:Hexachlorocyclohexane; C017967:W 7; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester