Journal
BRAIN RESEARCH
Volume 871, Issue 2, Pages 175-180Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(00)02430-6
Keywords
riluzole; spinal cord; glutamate uptake; amyotrophic lateral sclerosis; excitotoxicity; G protein
Categories
Funding
- NINDS NIH HHS [NS-30248] Funding Source: Medline
Ask authors/readers for more resources
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 mu M and 1.0 mu M riluzole, but not at the higher concentrations examined. Kinetics analysis demonstrated that riluzole (0.1 mu M) 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. (C) 2000 Elsevier Science B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available