Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes

R. D. Azbill, X. Mu, J. E. Springer

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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 μM and 1.0 μM riluzole, but not at the higher concentrations examined. Kinetics analysis demonstrated that riluzole (0.1 μM) 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. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalBrain Research
Volume871
Issue number2
DOIs
StatePublished - Jul 21 2000

Bibliographical note

Funding Information:
This work was supported by grants NS-30248 from the National Institutes of Health and SA-9502-K3 from the Kentucky Spinal Cord and Head Injury Research Trust to J.E.S.

Keywords

  • Amyotrophic lateral sclerosis
  • Excitotoxicity
  • G protein
  • Glutamate uptake
  • Riluzole
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes'. Together they form a unique fingerprint.

Cite this