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

Since increased tyrosine phosphorylation has been observed in response to b rain ischemia, we investigated whether riluzole tan inhibitor of glutamate neurotransmission with neuroprotective properties) affects tyrosine phospho rylation stimulated by N-methyl-D-aspartate (NMDA) in rat hippocampal slice s. Riluzole produced an extremely potent concentration-related inhibition o f NMDA (1 mM)-stimulated protein tyrosine phosphorylation (IC50=0.5+/-0.03 muM, 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 muM). These r esults suggest that inhibition of tyrosine phosphorylation may contribute t o the neuroprotective effects of riluzole against excitotoxic injury. (C) 2 001 Published by Elsevier Science B.V.