Riluzole increases glutamate uptake by cultured C6 astroglial cells.

Abstract

Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis (ALS) and may be effective for the treatment of other neurodegenerative and neuropsychiatric disorders. Riluzole exerts diverse actions on the central nervous system, including altering glutamate release and uptake, and therefore act diminishing glutamate extracellular levels, but the underlying mechanism of these actions is still unknown. Here, we demonstrate that riluzole stimulated glutamate uptake and augmented the expression of the glutamate EAAC1 transporter in C6 astroglial cell cultures. The effect of riluzole on glutamate uptake was reduced to below controls when it was co-administered with inhibitors of protein kinase C (PKC; bisindolylmaleimide II), phosphatidylinositol 3-kinase (PI3K; wortmannin) and fibroblast growth factor receptor 1 (FGFR1; PD173074). Riluzole also decreased reactive oxygen species load with no effect on glutathione levels. This study investigates three independent intracellular pathways and the mechanism of action of riluzole on glutamate metabolism.

• Authors: Oscar P Dall'Igna, Larissa D Bobermin, Diogo O Souza, André Quincozes-Santos
• Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (Int J Dev Neurosci) Vol. 31 Issue 7 Pg. 482-6 (Nov 2013) ISSN: 1873-474X [Electronic] United States
• PMID: 23777615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Excitatory Amino Acid Antagonists
• Excitatory Amino Acid Transporter 3
• Reactive Oxygen Species
• S100 Calcium Binding Protein beta Subunit
• S100b protein, rat
• Slc1a1 protein, rat
• Glutamic Acid
• Riluzole
• L-Lactate Dehydrogenase
• Glutathione

Topics

• Analysis of Variance
• Animals
• Astrocytes (drug effects, metabolism)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Antagonists (pharmacology)
• Excitatory Amino Acid Transporter 3 (metabolism)
• Glioma (pathology)
• Glutamic Acid (metabolism)
• Glutathione (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Riluzole (pharmacology)
• S100 Calcium Binding Protein beta Subunit (metabolism)
• Time Factors