FREE-RADICALS ENHANCE BASAL RELEASE OF D-[H-3]ASPARTATE FROM CEREBRALCORTICAL SYNAPTOSOMES

Excessive generation of free radicals has been implicated in several p athological conditions. We demonstrated previously that peroxide-gener ated free radicals decrease calcium-dependent high K+-evoked L-[H-3]gl utamate release from synaptosomes while increasing calcium-independent basal release. The present study evaluates the nonvesicular release o f excitatory amino acid neurotransmitters, using D-[H-3]aspartate as a n exogenous label of the cytoplasmic pool of L-glutamate and L-asparta te. Isolated presynaptic nerve terminals from the guinea pig cerebral cortex were used to examine the actions and interactions of peroxide, iron, and desferrioxamine. Pretreatment with peroxide, iron alone, or peroxide with iron significantly increased the calcium-independent bas al release of D-[H-3]aspartate. Pretreatment with desferrioxamine had little effect on its own but significantly limited the enhancement by peroxide. High K+-evoked release in the presence of Ca2+ was enhanced by peroxide but not by iron. These data suggest that peroxide increase s nonvesicular basal release of excitatory amino acids through Fenton- generated hydroxyl radicals. This release could cause accumulation of extracellular excitatory amino acids and contribute to the excitotoxic ity associated with some pathologies.