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Prolonged Inhibition of Glutamate Reuptake Down-Regulates NMDA Receptor Functions in Cultured Cerebellar Granule Cells.
- Source :
-
Journal of Neurochemistry . May99, Vol. 72 Issue 5, p2181-2190. 10p. 18 Graphs. - Publication Year :
- 1999
-
Abstract
- In the present study, we have examined the effects of prolonged (up to 72 h) inhibition of high-affinity glutamate reuptake by L-trans-pyrrolidine-2,4-dicarboxylate (PDC; 100 μM) on glutamate receptor functions in primary cultures of rat cerebellar granule neurons. This was done by comparing the effects of various glutamate receptor agonists on neuronal 45Ca2+ uptake, free cytoplasmic Ca2+ concentration ([Ca2+]i), and cell viability. We also determined the parameters of [3H]MK-801 binding as well as the expression of the NMDAR1 subunit protein in control and PDC-exposed cultures. The blockade of glutamate reuptake by PDC led to a gradual increase of ambient glutamate to concentrations that are neurotoxic when applied acutely to control cells. In PDC-exposed cells, however, the acute glutamate-induced NMDA receptor-mediated calcium fluxes were strongly diminished and no toxicity was observed. The down-regulation of the functional effects of glutamate was dependent on the duration of PDC exposure and was accompanied by a reduced NMDAR1 subunit expression and decreased [3H]MK-801 binding, indicative of a pronounced structural rearrangement of NMDA receptors. The possibility that the decrease of NMDA glutamate receptor sensitivity can be explained on the basis of a reduced density or altered subunit composition of NMDA receptors is discussed. [ABSTRACT FROM AUTHOR]
- Subjects :
- *METHYL aspartate
*CYTOPLASMIC granules
Subjects
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 72
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 6007035
- Full Text :
- https://doi.org/10.1046/j.1471-4159.1999.0722181.x