Free Radicals Enhance Basal Release of D-[exp 3H]Aspartate from Cerebral Cortical Synaptosomes
Abstract
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-[exp 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-[exp 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-[exp 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 Ca(exp 2+) 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1994
- Accession Number
- ADA531169
Entities
People
- Meta J. Bonner
- Sara C. Gilman
- Terry C. Pellmar
Organizations
- Armed Forces Radiobiology Research Institute