Oxygen free radicals regulate NMDA receptor function via a redox modulatory site

doi:10.1016/0896-6273(90)90343-E

Neuron

Volume 5, Issue 6, December 1990, Pages 841-846

https://doi.org/10.1016/0896-6273(90)90343-E Get rights and content

Abstract

A novel modulatory site on the N-methyl-d-aspartate (NMDA) receptor that is sensitive to sulfhydryl redox reagents was recently described. Here we report that this redox modulatory site is susceptible to oxidation by reactive oxygen species endogenous to the CNS. Oxygen free radicals generated by xanthine and xanthine oxidase were observed to decrease NMDA-induced changes in intracellular free Ca²⁺ concentrations and NMDA-evoked cation currents in cortical neurons in culture. Additionally, a sublethal production of free radicals by xanthine and xanthine oxidase reversed a dithiothreitol-induced enhancement of NMDA-mediated neurotoxicity in vitro. These results show that NMDA receptor function is modulated at its redox site by endogenous substances that normally accompany tissue reperfusion following an ischemic event. This novel mechanism for NMDA receptor regulation may have profound implications in the outcome of glutamate neurotoxicity in vivo.

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Neuron

Oxygen free radicals regulate NMDA receptor function via a redox modulatory site

Abstract

Neuron

Neurosci. Lett.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Neurosci. Lett.

Neuron

Brain Res.

J. Biol. Chem.

Neurosci. Lett.

Free Radic. Biol. Med.

Neurosci. Lett.

Trends Neurosci.

Brain Res.

Brain Res.

Brain Res.

Trends Pharmacol. Sci.

Responses mediated by excitatory amino acid receptors in solitary retinal ganglion cells from rat

J. Physiol.

Elevation of extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral dialysis

J. Neurochem.