title: Riluzole increases glutamate uptake by cultured C6 astroglial cells.
abstract: Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis (ALS) and may be effective for the treatment of other neurodegenerative and neuropsychiatric disorders. 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-administered with inhibitors of protein kinase C (PKC; bisindolylmaleimide II), phosphatidylinositol 3-kinase (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.
authors.affiliation: Rua Ramiro Barcelos 2600-Anexo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, CEP 90035-000, Brazil. Electronic address: oscarppd@yahoo.com.br.
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Dall'Igna
authors.forename: Larissa D
authors.initials: LD
authors.lastname: Bobermin
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005910:Glioma / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D050580:Excitatory Amino Acid Transporter 3; D017382:Reactive Oxygen Species; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; C493398:Slc1a1 protein, rat; D018698:Glutamic Acid; D019782:Riluzole; D007770:L-Lactate Dehydrogenase; D005978:Glutathione
keywords: ALS; ANOVA; BDNF; EAAT; EDTA; ERK; Excitotoxicity; FGFR substrate 2α; FGFR1; FRS2α; Fibroblast growth factor receptor 1; MAPK; MAPK/ERK; PI3K; PKC; Phosphatidylinositol 3-kinase; Protein kinase C; Riluzole; amyotrophic lateral sclerosis; analysis of variance; bis II; bisindolylmaleimide II; brain-derived neurotrophic factor; ethylene-diaminetetracetic acid; excitatory amino acid transporter; extracellular-signal regulated kinase; fibroblast growth factor receptor 1; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; protein kinase C