title: Potentiation of excito-toxicity by glutamate uptake inhibitor rather than glutamine synthetase inhibitor.
abstract: The neuroprotective functions of glia cells in the presence of excessive amounts of extracellular glutamate (Glu) were examined using glia-rich and glia-poor cultured cerebellar granule cells that contained the same number of neurons. In order to focus on the metabolic enzyme glutamine synthetase (GS) and the uptake system in glia cells, selective inhibitors such as L-methionine sulfoximine (MSO) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) were used as pharmacological tools. The increased amount of lactate dehydrogenase (LDH) leakage induced by 50 microM Glu and SITS was equivalent to that of 1 mM Glu. However, the simultaneous treatment with 50 microM Glu and 5 microM MSO did not increase the LDH leakage. The larger quantities of extracellular Glu were sustained in both glia-rich and glia-poor cultures. After the administration of Glu and MSO, however, the larger quantities of Glu were not sustained. Taking these results into consideration, the Glu uptake system in glia cells seems to be more important than the Glu metabolic enzyme system in the regulation of neuronal protection from Glu toxicity.
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D005970:Glutamate Synthase / Q000187:drug effects* / Q000378:metabolism*; D018698:Glutamic Acid / Q000009:adverse effects / Q000187:drug effects* / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D018698:Glutamic Acid; D005970:Glutamate Synthase