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. 1994 Sep;113(1):261–267. doi: 10.1111/j.1476-5381.1994.tb16203.x

Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured granule cells: evidence for a dual mechanism of action.

J P Hubert 1, J C Delumeau 1, J Glowinski 1, J Prémont 1, A Doble 1
PMCID: PMC1510058  PMID: 7812619

Abstract

1. Intracellular calcium levels were measured in cultured cerebellar granule cells of the rat by use of the fluorescent dye, indo-1/AM. 2. Intracellular calcium levels were increased by depolarizing stimuli such as N-methyl-D-aspartate (NMDA) (100 microM), glutamic acid (20 microM), and veratridine (10 microM). This increase was essentially due to entry of external calcium. 3. Riluzole (10 microM) blocked responses to all the depolarizing agents. 4. Riluzole could still block the increase in intracellular calcium evoked by NMDA or glutamic acid when sodium channels were blocked by tetrodotoxin, suggesting that this effect is not mediated by a direct action of riluzole on the voltage-dependent sodium channel. 5. Pretreatment of the cells with pertussis toxin (0.1 micrograms ml-1) did not modify the increases in intracellular calcium evoked by NMDA, glutamic acid or veratridine. 6. In pertussis toxin-treated cells, riluzole could no longer block responses to excitatory amino acids, but still blocked responses to veratridine. 7. It is concluded that riluzole has a dual action on cerebellar granule cells, both blocking voltage-dependent sodium channels and interfering with NMDA receptor-mediated responses via a pertussis toxin-sensitive mechanism. Furthermore, these two processes have been shown to be independent.

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Selected References

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  1. Becquet D., Faudon M., Hery F. Effect of thalamic parafascicularis nucleus stimulation in regulation of serotoninergic transmission in the cat caudate nucleus: involvement of autoreceptors in the dorsalis raphe nucleus. Neuroscience. 1989;33(2):293–300. doi: 10.1016/0306-4522(89)90209-1. [DOI] [PubMed] [Google Scholar]
  2. Becquet D., Faudon M., Hery F. In vivo evidence for an inhibitory glutamatergic control of serotonin release in the cat caudate nucleus: involvement of GABA neurons. Brain Res. 1990 Jun 11;519(1-2):82–88. doi: 10.1016/0006-8993(90)90063-h. [DOI] [PubMed] [Google Scholar]
  3. Ben-Ari Y., Aniksztejn L., Bregestovski P. Protein kinase C modulation of NMDA currents: an important link for LTP induction. Trends Neurosci. 1992 Sep;15(9):333–339. doi: 10.1016/0166-2236(92)90049-e. [DOI] [PubMed] [Google Scholar]
  4. Benavides J., Camelin J. C., Mitrani N., Flamand F., Uzan A., Legrand J. J., Gueremy C., Le Fur G. 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--II. Biochemical properties. Neuropharmacology. 1985 Nov;24(11):1085–1092. doi: 10.1016/0028-3908(85)90196-0. [DOI] [PubMed] [Google Scholar]
  5. Bensimon G., Lacomblez L., Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585–591. doi: 10.1056/NEJM199403033300901. [DOI] [PubMed] [Google Scholar]
  6. Bom A. H., Heiligers J. P., Saxena P. R., Verdouw P. D. Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors. Br J Pharmacol. 1989 Jun;97(2):383–390. doi: 10.1111/j.1476-5381.1989.tb11965.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chéramy A., Barbeito L., Godeheu G., Glowinski J. Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo. Neurosci Lett. 1992 Dec 7;147(2):209–212. doi: 10.1016/0304-3940(92)90597-z. [DOI] [PubMed] [Google Scholar]
  8. Debono M. W., Le Guern J., Canton T., Doble A., Pradier L. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. Eur J Pharmacol. 1993 Apr 28;235(2-3):283–289. doi: 10.1016/0014-2999(93)90147-a. [DOI] [PubMed] [Google Scholar]
  9. Delumeau Jean C., Tencé Martine, Marin Philippe, Cordier Jocelyne, Glowinski Jacques, Prémont Joël. Synergistic Regulation of Cytosolic Ca2+ Concentration by Adenosine and alpha1-Adrenergic Agonists in Mouse Striatal Astrocytes. Eur J Neurosci. 1991 Jun;3(6):539–550. doi: 10.1111/j.1460-9568.1991.tb00841.x. [DOI] [PubMed] [Google Scholar]
  10. Doble A., Hubert J. P., Blanchard J. C. Pertussis toxin pretreatment abolishes the inhibitory effect of riluzole and carbachol on D-[3H]aspartate release from cultured cerebellar granule cells. Neurosci Lett. 1992 Jun 22;140(2):251–254. doi: 10.1016/0304-3940(92)90114-m. [DOI] [PubMed] [Google Scholar]
  11. Drejer J., Honoré T., Meier E., Schousboe A. Pharmacologically distinct glutamate receptors on cerebellar granule cells. Life Sci. 1986 Jun 9;38(23):2077–2085. doi: 10.1016/0024-3205(86)90206-7. [DOI] [PubMed] [Google Scholar]
  12. Drejer J., Honoré T., Schousboe A. Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. J Neurosci. 1987 Sep;7(9):2910–2916. doi: 10.1523/JNEUROSCI.07-09-02910.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frandsen A., Drejer J., Schousboe A. Glutamate-induced 45Ca2+ uptake into immature cerebral cortex neurons shows a distinct pharmacological profile. J Neurochem. 1989 Dec;53(6):1959–1962. doi: 10.1111/j.1471-4159.1989.tb09268.x. [DOI] [PubMed] [Google Scholar]
  14. Gallo V., Ciotti M. T., Coletti A., Aloisi F., Levi G. Selective release of glutamate from cerebellar granule cells differentiating in culture. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7919–7923. doi: 10.1073/pnas.79.24.7919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  16. Hubert J. P., Doble A. Ibotenic acid stimulates D-[3H]aspartate release from cultured cerebellar granule cells. Neurosci Lett. 1989 Jan 30;96(3):345–350. doi: 10.1016/0304-3940(89)90403-5. [DOI] [PubMed] [Google Scholar]
  17. Irving A. J., Collingridge G. L., Schofield J. G. Interactions between Ca2+ mobilizing mechanisms in cultured rat cerebellar granule cells. J Physiol. 1992 Oct;456:667–680. doi: 10.1113/jphysiol.1992.sp019360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malgouris C., Bardot F., Daniel M., Pellis F., Rataud J., Uzan A., Blanchard J. C., Laduron P. M. Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils. J Neurosci. 1989 Nov;9(11):3720–3727. doi: 10.1523/JNEUROSCI.09-11-03720.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martin D., Thompson M. A., Nadler J. V. The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol. 1993 Dec 21;250(3):473–476. doi: 10.1016/0014-2999(93)90037-i. [DOI] [PubMed] [Google Scholar]
  20. Mizoule J., Meldrum B., Mazadier M., Croucher M., Ollat C., Uzan A., Legrand J. J., Gueremy C., Le Fur G. 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--I. Anticonvulsant properties. Neuropharmacology. 1985 Aug;24(8):767–773. doi: 10.1016/0028-3908(85)90011-5. [DOI] [PubMed] [Google Scholar]
  21. Mollard P., Guerineau N., Audin J., Dufy B. Measurement of CA2+ transients using simultaneous dual-emission microspectrofluorimetry and electrophysiology in individual pituitary cells. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1045–1052. doi: 10.1016/0006-291x(89)91775-0. [DOI] [PubMed] [Google Scholar]
  22. Pearson H., Graham M. E., Burgoyne R. D. N-methyl-D-aspartate responses in rat cerebellar granule cells are modified by chronic depolarisation in culture. Neurosci Lett. 1992 Aug 3;142(1):27–30. doi: 10.1016/0304-3940(92)90612-b. [DOI] [PubMed] [Google Scholar]
  23. Schieren I., MacDermott A. Flow cytometric identification and purification of cells by ligand-induced changes in intracellular calcium. J Neurosci Methods. 1988 Nov;26(1):35–44. doi: 10.1016/0165-0270(88)90127-6. [DOI] [PubMed] [Google Scholar]
  24. Simpson P. B., Challiss R. A., Nahorski S. R. Involvement of intracellular stores in the Ca2+ responses to N-Methyl-D-aspartate and depolarization in cerebellar granule cells. J Neurochem. 1993 Aug;61(2):760–763. doi: 10.1111/j.1471-4159.1993.tb02184.x. [DOI] [PubMed] [Google Scholar]
  25. Zhao Z., Peng L. Glutamate effects on calcium homeostasis in cerebellar granule cells in primary cultures grown under depolarizing and nondepolarizing conditions. Synapse. 1993 Apr;13(4):315–321. doi: 10.1002/syn.890130404. [DOI] [PubMed] [Google Scholar]

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