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 μM) riluzole significantly increased glutamate uptake, whereas from 100 μM promoted a slight reduction.
4. Considering the large range of glutamate levels in the synaptic cleft, we studied the 1 μM riluzole effect on uptake of glutamate at different concentrations (1–1000 μM). Riluzole was more effective at low glutamate concentrations (10 μM), 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Anderson, C. M., and Swanson, R. A. (2000). Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 32: (1) 1-14.
Azbill, R. D., Mu, X., and Springer, J. E. (2000). Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res. 871:175-180.
Bodner, Th., Jenner, C., Benke, Th., Ober, A., Seppi, K., and Fleischhacker, W. W. (2001). Intoxication with riluzole in Huntington's disease. Neurology 57:1141-1143.
Danbolt, N. C. (2001). Glutamate uptake. Prog. Neurobiol. 65:1-105.
Doble, A. (1996). The pharmacology and mechanism of action of riluzole. Neurology 47(4):233S-241S.
Dunlop, J., McIlvain, H. B., She, Y., and Howland, D. S. (2003). Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. J. Neurosci. 23(5):1688-1695.
Frizzo, M. E. S., Lara, D. R., Dahm, K. C. S., Prokopiuk, A. S., Swanson, R. A., and Souza, D. O. (2001). Activation of glutamate uptake by guanosine in primary astrocyte cultures. Neuroreport 12:879-881.
Lowry, O. H., Rosebrough, N. H., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265-275.
Maragakis, N. J., and Rothstein, J. D. (2001). Glutamate transporters in neurologic disease. Arch. Neurol. 58:365-370.
Pena, F., and Tapia, R. (2000). Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: Role of glutamate-and GABA-mediated neurotransmission and of ion channels. Neuroscience 101(3):547-561.
Zelenaia, O., Schlag, B. D., Gochenauer, G. E., Ganel, R., Song, W., Beesley, J. S., Grinspan, J. B., Rothstein, J. D., and Robinson, M. B. (2000). Epidermal growth factor receptor agonists increase expression of glutamate transporter GLT-1 in astrocytes through pathways dependent on phosphatidylinositol 3-kinase and transcription factor NF-kB. Mol. Pharmacol. 57:667-678.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Frizzo, M.E.d.S., Dall'Onder, L.P., Dalcin, K.B. et al. Riluzole Enhances Glutamate Uptake in Rat Astrocyte Cultures. Cell Mol Neurobiol 24, 123–128 (2004). https://doi.org/10.1023/B:CEMN.0000012717.37839.07
Issue Date:
DOI: https://doi.org/10.1023/B:CEMN.0000012717.37839.07