Effect of oxidative stress on excitatory amino acid release by cerebral cortical synaptosomes.
Previous studies in our laboratory have suggested that an oxidation reaction is responsible for the actions of free radicals to decrease synaptic potentials. Recently we observed that free radicals both decreased depolarization-induced vesicular release and enhanced basal, nonvesicular release of the excitatory amino acid, [3H]L-glutamate. In order to evaluate the contribution of oxidative reactions to this latter effect, we evaluated the actions of the oxidizing agent chloramine-T on synaptosomal release of excitatory amino acids, using [3H]D-aspartate as the exogenous label. Basal and depolarization evoked [3H]D-aspartate release were calcium-independent and nonvesicular. Chloramine-T pretreatment significantly increased basal release, while having no effect on high K(+)-evoked release. These data suggest that an oxidative process can mimic the free radical increase of basal release, as well as the decrease in synaptic potentials. On the other hand, the calcium-independent-evoked release may involve a different mechanism. Our results demonstrate that under basal, nondepolarizing conditions, oxidative stress exerts an adverse effect on the presynaptic nerve terminal, resulting in an increased release of potentially damaging excitatory amino acid neurotransmitters.
Gilman
S C
SC
Department of Physiology Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603.
Bonner
M J
MJ
Pellmar
T C
TC
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002700:Chloramines / Q000494:pharmacology; D005609:Free Radicals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D009435:Synaptic Transmission; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology
D000596:Amino Acids; D002700:Chloramines; D005609:Free Radicals; D018377:Neurotransmitter Agents; D016877:Oxidants; D014105:Tosyl Compounds; C016300:chloramine-T; D001224:Aspartic Acid