Source:http://linkedlifedata.com/resource/pubmed/id/15072265
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2004-4-9
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GABA-A Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Gabra6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Kainic Acid
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pubmed:status |
MEDLINE
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pubmed:issn |
1473-4222
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27-38
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15072265-Animals,
pubmed-meshheading:15072265-Cells, Cultured,
pubmed-meshheading:15072265-Cerebellum,
pubmed-meshheading:15072265-Dose-Response Relationship, Drug,
pubmed-meshheading:15072265-Down-Regulation,
pubmed-meshheading:15072265-GABA-A Receptor Antagonists,
pubmed-meshheading:15072265-Kainic Acid,
pubmed-meshheading:15072265-Mice,
pubmed-meshheading:15072265-Mice, Inbred C57BL,
pubmed-meshheading:15072265-Mice, Knockout,
pubmed-meshheading:15072265-Receptors, GABA-A,
pubmed-meshheading:15072265-Receptors, Kainic Acid
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pubmed:year |
2004
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pubmed:articleTitle |
Kainate down-regulates a subset of GABAA receptor subunits expressed in cultured mouse cerebellar granule cells.
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pubmed:affiliation |
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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