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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-4-9
pubmed:abstractText
The effect of kainate, an agonist selective for ionotropic AMPA/kainate type of glutamate receptors, on GABAA receptor subunit expression in cultured mouse cerebellar granule cells was studied using quantitative RT-PCR, ligand binding and electrophysiology. Chronic kainate treatment, without producing excitotoxicity, resulted in preferential, dose- and time-dependent down-regulation of alpha1, alpha6 and beta2 subunit mRNA expression, the expression of beta3, gamma2 and delta subunit mRNAs being less affected. The down-regulation was reversed by DNQX, an AMPA/kainate-selective glutamate receptor antagonist. A 14-day kainate treatment resulted in 46% decrease of total [3H]Ro 15-4513 binding to the benzodiazepine sites. Diazepam-insensitive [3H]Ro 15-4513 binding was decreased by 89% in accordance with very low amount of alpha6 subunit mRNA present. Diazepam-sensitive [3H]Ro 154513 binding was decreased only by 40%, contrasting >90% decrease in alpha1 subunit mRNA expression. However, this was consistent with lower potentiation of GABA-evoked currents in kainate-treated than control cells by the alpha1-selective benzodiazepine site ligand zolpidem, suggesting compensatory expression of alpha5 (and/or alpha2 or alpha3) subunits producing diazepam-sensitive but zolpidem-insensitive receptor subtypes. In conclusion, chronic kainate treatment of cerebellar granule cells selectively down-regulates oil, alpha6 and beta2 subunits resulting in altered GABAA receptor pharmacology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1473-4222
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-38
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Kainate down-regulates a subset of GABAA receptor subunits expressed in cultured mouse cerebellar granule cells.
pubmed:affiliation
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't