Alteration in Neuronal‐Glial Metabolism of Glutamate by the Neurotoxin Kainic Acid

Abstract

The effect of the excitotoxin kainic acid on glutamate and glutamine metabolism was studied in [rat] cerebellar slices incubated with D-[2-14C]glucose, [U[uniformly labeled]-14C]GABA, [3H]acetate, [U-14C]glutamate and [U-14C]glutamine as precursors. Kainic acid (1 mM) strongly inhibited the labeling of glutamine relative to that of glutamate from all precursors except [2-14C]glucose and [U-14C]glutamine. Kainic acid did not inhibit glutamine synthetase directly. In the cerebellum, kainic acid apparently inhibits the synthesis of glutamine from the small pool of glutamate that is thought to be associated with glial cells. Kainic acid also markedly stimulated the efflux of glutamate from cerebellar slices and this release was not sensitive to tetrodotoxin. Kainic acid stimulated efflux of both glucose- and acetate-labeled glutamate. Veratridine released glucose-labeled glutamate preferentially via a tetrodotoxin-sensitive mechanism. Kainic acid did not release [U-14C]glutamate from synaptosomal fractions. The bulk of the glutamate released from cerebellar slices by kainic acid probably comes from nonsynaptic pools.