Antagonism by Riluzole of Entry of Calcium Evoked by NMDA and Veratridine in Rat Cultured Granule Cells: Evidence for a Dual Mechanism of Action

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1994 Sep 1

PMID 7812619

Citations 19

Authors

J P Hubert

J C Delumeau

J Glowinski

J Premont

A Doble

Affiliations

Soon will be listed here.

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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References

Doble A, Hubert J, Blanchard J . Pertussis toxin pretreatment abolishes the inhibitory effect of riluzole and carbachol on D-[3H]aspartate release from cultured cerebellar granule cells. Neurosci Lett. 1992; 140(2):251-4. DOI: 10.1016/0304-3940(92)90114-m. View

MIZOULE J, Meldrum B, Mazadier M, Croucher M, Ollat C, Uzan A . 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--I. Anticonvulsant properties. Neuropharmacology. 1985; 24(8):767-73. DOI: 10.1016/0028-3908(85)90011-5. View

Delumeau J, Tence M, Marin P, Cordier J, Glowinski J, Premont J . Synergistic Regulation of Cytosolic Ca2+ Concentration by Adenosine and alpha1-Adrenergic Agonists in Mouse Striatal Astrocytes. Eur J Neurosci. 1991; 3(6):539-550. DOI: 10.1111/j.1460-9568.1991.tb00841.x. View

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; 164(3):1045-52. DOI: 10.1016/0006-291x(89)91775-0. View

Benavides J, Camelin J, Mitrani N, Flamand F, Uzan A, Legrand J . 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--II. Biochemical properties. Neuropharmacology. 1985; 24(11):1085-92. DOI: 10.1016/0028-3908(85)90196-0. View

Gallo V, Ciotti M, 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; 79(24):7919-23. PMC: 347461. DOI: 10.1073/pnas.79.24.7919. View

Drejer J, Honore T, Meier E, Schousboe A . Pharmacologically distinct glutamate receptors on cerebellar granule cells. Life Sci. 1986; 38(23):2077-85. DOI: 10.1016/0024-3205(86)90206-7. View

Irving A, Collingridge G, Schofield J . Interactions between Ca2+ mobilizing mechanisms in cultured rat cerebellar granule cells. J Physiol. 1992; 456:667-80. PMC: 1175705. DOI: 10.1113/jphysiol.1992.sp019360. View

Ben-Ari Y, Aniksztejn L, Bregestovski P . Protein kinase C modulation of NMDA currents: an important link for LTP induction. Trends Neurosci. 1992; 15(9):333-9. DOI: 10.1016/0166-2236(92)90049-e. View

10.

Malgouris C, Bardot F, Daniel M, Pellis F, Rataud J, Uzan A . Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils. J Neurosci. 1989; 9(11):3720-7. PMC: 6569943. View

11.

Hubert J, Doble A . Ibotenic acid stimulates D-[3H]aspartate release from cultured cerebellar granule cells. Neurosci Lett. 1989; 96(3):345-50. DOI: 10.1016/0304-3940(89)90403-5. View

12.

Cheramy 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; 147(2):209-12. DOI: 10.1016/0304-3940(92)90597-z. View

13.

Pearson H, Graham M, Burgoyne R . N-methyl-D-aspartate responses in rat cerebellar granule cells are modified by chronic depolarisation in culture. Neurosci Lett. 1992; 142(1):27-30. DOI: 10.1016/0304-3940(92)90612-b. View

14.

Frandsen A, Drejer J, Schousboe A . Glutamate-induced 45Ca2+ uptake into immature cerebral cortex neurons shows a distinct pharmacological profile. J Neurochem. 1989; 53(6):1959-62. DOI: 10.1111/j.1471-4159.1989.tb09268.x. View

15.

Drejer J, Honore T, Schousboe A . Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. J Neurosci. 1987; 7(9):2910-6. PMC: 6569133. View

16.

Schieren I, Macdermott A . Flow cytometric identification and purification of cells by ligand-induced changes in intracellular calcium. J Neurosci Methods. 1988; 26(1):35-44. DOI: 10.1016/0165-0270(88)90127-6. View

17.

Grynkiewicz G, Poenie M, Tsien R . A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985; 260(6):3440-50. View

18.

Zhao Z, Peng L . Glutamate effects on calcium homeostasis in cerebellar granule cells in primary cultures grown under depolarizing and nondepolarizing conditions. Synapse. 1993; 13(4):315-21. DOI: 10.1002/syn.890130404. View

19.

Simpson P, Challiss R, Nahorski S . Involvement of intracellular stores in the Ca2+ responses to N-Methyl-D-aspartate and depolarization in cerebellar granule cells. J Neurochem. 1993; 61(2):760-3. DOI: 10.1111/j.1471-4159.1993.tb02184.x. View

20.

Martin D, Thompson M, Nadler J . The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol. 1993; 250(3):473-6. DOI: 10.1016/0014-2999(93)90037-i. View