title: Riluzole enhances glutamate uptake in rat astrocyte cultures.
abstract: 1. Riluzole is used for the treatment of amyotrophic lateral sclerosis and reported to have neuroprotective effects in animal models of Parkinson's disease, Huntington's disease, and brain ischemia. The neuroprotective action of riluzole has been attributed to its ability to inhibit glutamate release (A. Doble, Neurology 47(4):233S-241S, 1996). 2. The effect of riluzole on L-[2,3-3H] glutamate uptake was investigated in rat cortical astrocyte cultures. 3. Riluzole showed a biphasic concentration-dependent effect on basal glutamate uptake. At low concentrations (1 and 10 microM) riluzole significantly increased glutamate uptake, whereas from 100 microM promoted a slight reduction. 4. Considering the large range of glutamate levels in the synaptic cleft, we studied the 1 microM riluzole effect on uptake of glutamate at different concentrations (1-1000 microM). Riluzole was more effective at low glutamate concentrations (10 microM), enhancing the basal glutamate uptake up to 42%. 5. The action of riluzole on astrocytic glutamate uptake could be an additional mechanism to its neuroprotective role, perhaps suggesting a modulatory action on glutamatergic system involving glutamate clearance from synaptic cleft.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. frizzo@ufrgs.br
authors.forename: Marcos Emílio dos Santos
authors.initials: ME
authors.lastname: Frizzo
authors.forename: Leonara Patrícia
authors.initials: LP
authors.lastname: Dall'Onder
authors.forename: Karina Borges
authors.initials: KB
authors.lastname: Dalcin
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019782:Riluzole