EFFECT OF OXIDATIVE STRESS ON EXCITATORY AMINO-ACID RELEASE BY CEREBRAL CORTICAL SYNAPTOSOMES

Previous studies in our laboratory have suggested that an oxidation re action is responsible for the actions of free radicals to decrease syn aptic Potentials. Recently we observed that free radicals both decreas ed depolarization-induced vesicular release and enhanced basal, nonves icular release of the excitatory amino acid, [H-3]L-glutamate. In orde r to evaluate the contribution of oxidative reactions to this latter e ffect, we evaluated the actions of the oxidizing agent chloramine-T on synaptosomal release of excitatory amino acids, using [H-3]D-aspartat e as the exogenous label. Basal and depolarization evoked [H-3]D-aspar tate release were calcium-independent and nonvesicular. Chloramine-T p retreatment significantly increased basal release, while having no eff ect on high K+-evoked release. These data suggest that an oxidative pr ocess can mimic the free radical increase of basal release, as well as the decrease in synaptic potentials. On the other hand, the calcium-i ndependent-evoked release may involve a different mechanism. Our resul ts demonstrate that under basal, nondepolarizing conditions, oxidative stress exerts an adverse effect on the presynaptic nerve terminal, re sulting in an increased release of potentially damaging excitatory ami no acid neurotransmitters.