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Riluzole exerts diverse actions on the central nervous system, including altering glutamate release and uptake, and therefore act diminishing glutamate extracellular levels, but the underlying mechanism of these actions is still unknown. Here, we demonstrate that riluzole stimulated glutamate uptake and augmented the expression of the glutamate EAAC1 transporter in C6 astroglial cell cultures. The effect of riluzole on glutamate uptake was reduced to below controls when it was co\u2010administered with inhibitors of protein kinase C (PKC; bisindolylmaleimide II), phosphatidylinositol 3\u2010kinase (PI3K; wortmannin) and fibroblast growth factor receptor 1 (FGFR1; PD173074). Riluzole also decreased reactive oxygen species load with no effect on glutathione levels. This study investigates three independent intracellular pathways and the mechanism of action of riluzole on glutamate metabolism.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2013.06.002","type":"journal-article","created":{"date-parts":[[2013,6,15]],"date-time":"2013-06-15T16:16:05Z","timestamp":1371312965000},"page":"482-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Riluzole increases glutamate uptake by cultured C6 astroglial cells"],"prefix":"10.1002","volume":"31","author":[{"given":"Oscar P.","family":"Dall'Igna","sequence":"first","affiliation":[{"name":"Rua Ramiro Barcelos 2600\u2010Anexo, Departamento de Bioqu\u00edmica Universidade Federal do Rio Grande do Sul Porto Alegre CEP 90035\u2010000 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa D.","family":"Bobermin","sequence":"additional","affiliation":[{"name":"Rua Ramiro Barcelos 2600\u2010Anexo, Departamento de 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