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

被引:141
作者
Azbill, RD [1 ]
Mu, X [1 ]
Springer, JE [1 ]
机构
[1] Univ Kentucky, Med Ctr, Spinal Cord & Brain Injury Res Ctr, Dept Neurobiol & Anat, Lexington, KY 40536 USA
关键词
riluzole; spinal cord; glutamate uptake; amyotrophic lateral sclerosis; excitotoxicity; G protein;
D O I
10.1016/S0006-8993(00)02430-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:175 / 180
页数:6
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