Free radicals enhance basal release of D-[3H]aspartate from cerebral cortical synaptosomes.
Excessive generation of free radicals has been implicated in several pathological conditions. We demonstrated previously that peroxide-generated free radicals decrease calcium-dependent high K(+)-evoked L[3H]-glutamate release from synaptosomes while increasing calcium-independent basal release. The present study evaluates the nonvesicular release of excitatory amino acid neurotransmitters, using D-[3H]aspartate as an exogenous label of the cytoplasmic pool of L-glutamate and L-aspartate. 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 basal release of D-[3H]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 increases 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 excitotoxicity associated with some pathologies.
Gilman
S C
SC
Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603.
Bonner
M J
MJ
Pellmar
T C
TC
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology; D008297:Male; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D005609:Free Radicals; D014316:Tritium; D001224:Aspartic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D003676:Deferoxamine; D002118:Calcium