Effects of riluzole on N-methyl-D-aspartate-induced tyrosine phosphorylation in the rat hippocampus

Brain Res. 2001 Jun 8;903(1-2):222-5. doi: 10.1016/s0006-8993(01)02429-5.

Abstract

Since increased tyrosine phosphorylation has been observed in response to brain ischemia, we investigated whether riluzole (an inhibitor of glutamate neurotransmission with neuroprotective properties) affects tyrosine phosphorylation stimulated by N-methyl-D-aspartate (NMDA) in rat hippocampal slices. Riluzole produced an extremely potent concentration-related inhibition of NMDA (1 mM)-stimulated protein tyrosine phosphorylation (IC(50)=0.5+/-0.03 microM, mean+/-S.D.), but failed to affect that evoked by phorbol 12-myristate 13-acetate (PMA, an activator of protein kinase C, 0.1 and 1 microM). These results suggest that inhibition of tyrosine phosphorylation may contribute to the neuroprotective effects of riluzole against excitotoxic injury.

MeSH terms

  • Animals
  • Carcinogens / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • N-Methylaspartate / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / metabolism
  • Riluzole / pharmacology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tyrosine / metabolism*

Substances

  • Carcinogens
  • Excitatory Amino Acid Agonists
  • Neuroprotective Agents
  • Neurotoxins
  • Receptors, Glutamate
  • Tyrosine
  • N-Methylaspartate
  • Riluzole
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate