title: Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes.
abstract: The purpose of this study was to examine the effect of the anti-convulsant agent, riluzole, on high-affinity glutamate uptake as measured in rat spinal cord synaptosomes. The rate of glutamate uptake was significantly increased in the presence of 0.1 microM and 1.0 microM riluzole, but not at the higher concentrations examined. Kinetics analysis demonstrated that riluzole (0.1 microM) decreased the apparent K(m) by 21% and increased the V(max) by 31%. Glutamate uptake also was significantly increased in spinal cord synaptosomes obtained from rats treated with 8 mg/kg (i.p.) of riluzole and sacrificed 4 h later. The increase in glutamate uptake in vitro was not affected by pretreatment either with H7, an inhibitor of PKA and PKC, or with the PKC activating phorbol ester, 12-O-tetradecanoylphorbol 13-acetate. Previous studies have shown that some of the actions of riluzole are mediated by G proteins sensitive to pertussis toxin. Surprisingly, treatment of synaptosomes with pertussis toxin alone increased the rate of glutamate uptake, while having no effect on uptake in the presence of riluzole. However, pretreatment with cholera toxin was found to completely block the effects of riluzole on glutamate uptake. These results reveal an additional mechanism by which riluzole can affect glutamatergic neurotransmission, and provides further support that riluzole may prove beneficial in the treatment of traumatic central nervous system injuries involving the excitotoxic actions of glutamate.
authors.affiliation: Department of Anatomy and Neurobiology, Spinal Cord and Brain Injury Research Center, University of Kentucky Medical Center, Lexington, KY 40536-0084, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Azbill
authors.forename: X
authors.initials: X
authors.lastname: Mu
authors.forename: J E
authors.initials: JE
authors.lastname: Springer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D051381:Rats; D020318:Rats, Long-Evans; D019782:Riluzole / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid; D019782:Riluzole; D019204:GTP-Binding Proteins