Effects of riluzole on electrically evoked neurotransmitter release
- 1 July 2000
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 130 (6), 1227-1234
- https://doi.org/10.1038/sj.bjp.0703424
Abstract
1. The main purpose of the present study was to investigate the effects of the neuroprotective agent riluzole on the electrically evoked release of [(3)H]-glutamate ([(3)H]-Glu) in mouse neocortical slices. The reported selectivity of riluzole for excitatory amino acids was tested in release experiments with further neurotransmitters. Also distinct species, mouse, rat and man were compared. 2. [(3)H]-Glu was formed endogenously during incubation of slices with [(3)H]-glutamine ([(3)H]-Gln). Released [(3)H]-Glu and tissue [(3)H]-Glu was separated by anion exchange chromatography. Electrically evoked [(3)H]-Glu release was strongly diminished by tetrodotoxin (TTX) and Ca(2+)-withdrawal. 3. Riluzole (100 microM) depressed the release of [(3)H]-Glu up to 77% (IC(50)=19.5 microM). Riluzole was also able to inhibit strongly the electrically evoked release of [(3)H]-acetylcholine ([(3)H]-ACh) (at 100 microM by 92%, IC(50)=3.3 microM, and [(3)H]-dopamine ([(3)H]-DA) (at 32 microM by 72%, IC(50)=6.8 microM). However, the release of [(3)H]-serotonin ([(3)H]-5-HT) was less diminished (at 100 microM by 53%, IC(50)=39.8 microM). Riluzole up to 100 microM did not affect [(3)H]-noradrenaline ([(3)H]-NA) release. 4. Between species, i.e. in mouse, rat and human neocortex, no significant differences between the effects of riluzole could be observed. 5. The NMDA-receptor blocker MK-801 (1 microM) and the AMPA/Kainate-receptor blocker NBQX (1 microM) did neither affect the electrically evoked [(3)H]-ACh release nor its inhibition by riluzole, indicating that effects of riluzole on transmitter release were neither due to modulation of ionotropic Glu receptors, nor due to indirect inhibition of Glu release through these receptors. 6. Taken together, riluzole inhibits the release of distinct neurotransmitters differently, but is not selective for the excitatory amino acid Glu.This publication has 41 references indexed in Scilit:
- Ouabain-induced Increase in Dopamine Release from Mouse Striatal Slices is Antagonized by RiluzoleJournal of Pharmacy and Pharmacology, 1998
- Glutamate release inhibitors: A critical assessment of their action mechanismAmino Acids, 1998
- Riluzole AnesthesiaAnesthesiology, 1996
- A Controlled Trial of Riluzole in Amyotrophic Lateral SclerosisThe New England Journal of Medicine, 1994
- Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivoNeuroscience Letters, 1992
- Pertussis toxin pretreatment abolishes the inhibitory effect of riluzole and carbachol on d[3H]aspartate release from cultured cerebellar granule cellsNeuroscience Letters, 1992
- Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemiaNeuroscience Letters, 1992
- Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptakeNature, 1990
- Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanismsTrends in Pharmacological Sciences, 1988
- GLUTAMINE—A MAJOR SUBSTRATE FOR NERVE ENDINGSJournal of Neurochemistry, 1978