Excitatory Amino Acid-Elicited Tonic Convulsions in Mice and N-Methyl-D-Aspartate Receptor Activation: Role of Ca2+ Influx and Involvement of Intracellular Ca2+-Dependent Biochemical Processes
| Autor: | Nobuhide Akaike, Norio Himori |
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| Rok vydání: | 2002 |
| Předmět: | |
| Zdroj: | Pharmacology. 66:136-143 |
| ISSN: | 1423-0313 0031-7012 |
| DOI: | 10.1159/000063795 |
| Popis: | Intravenously administered nimodipine (an L-type Ca2+ antagonist) as well as dizocilpine (an N-methyl-D-aspartate – NMDA – antagonist) showed a wide spectrum of anticonvulsant activity in intracerebroventricular mouse models for excessive activation of excitatory amino acid receptors. The duration of Bay k-8644 (L-type Ca2+ agonist; intracerebroventricular administration) caused seizures was significantly reduced by intravenously administered nimodipine. Intracisternal administration of Bay k-8644 lowered the convulsion threshold of an intracerebroventricular injection of NMDA. Intracisternal administration of ω-conotoxin GVIA (N-type Ca2+ antagonist) only tended to inhibit the NMDA-induced tonic convulsions. Intracisternal administration of staurosporine (a protein kinase C inhibitor) or calmidazolium (a calmodulin antagonist) was effective in inhibiting the NMDA-induced tonic convulsions. Calmidazolium, unlike staurosporine, produced side effects at a dose showing its anticonvulsant activity. From these results, it is suggested that excessive activation of excitatory amino acid receptors results in tonic convulsions by virtue of a massive increase of Ca2+ influx mainly through NMDA receptor channels, and at least in part through L-type Ca2+ channels, and in subsequent activation of protein kinase C and possibly calmodulin. |
| Databáze: | OpenAIRE |
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