Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-5-8
pubmed:abstractText
To clarify the mechanisms of the pharmacological action of carbamazepine (CBZ), we determined the effect of CBZ on GABA and glutamate release associated with the ryanodine receptor (Ryr)-sensitive Ca(2+)-induced Ca(2+)-releasing system (CICR) in the rat hippocampus using microdialysis. The therapeutically relevant concentration of CBZ increased basal GABA release without affecting basal glutamate release; however, K(+)-evoked releases were concentration-dependently reduced by CBZ. Lower-concentration ryanodine increased basal and K(+)-evoked releases of GABA and glutamate in a concentration dependent manner, whereas higher-concentration ryanodine reduced them. These inflection points in the concentration-response curves of ryanodine for neurotransmitter release (critical concentrations) were shifted to the left by K(+)-evoked stimulation. The critical concentration of ryanodine in GABA release was lower than that in glutamate release. During the resting stage, the critical concentrations of ryanodine were unaffected by inhibition of L-type, N-type and P-type voltage-sensitive Ca(2+) channels (VSCCs) but were prevented by CBZ; however, during the neuronal hyperexcitable stage, the critical concentration was increased by CBZ, L-type and P-type VSCC inhibitors but not the N-type VSCC inhibitor. Therefore, a therapeutically relevant concentration of CBZ protects against the breakdown of the neurotransmitter release mechanism induced by hyperactivation of Ryr via inhibition of L-type and P-type VSCCs as well as inhibition of Ryr-sensitive CICR. These actions of CBZ appear to be involved, at least partially, in its anti-seizure mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1538-46
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Carbamazepine prevents breakdown of neurotransmitter release induced by hyperactivation of ryanodine receptor.
pubmed:affiliation
Department of Neuropsychiatry, Hirosaki University, Hirosaki, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't