MODULATION OF N-METHYL-D-ASPARTATE RECEPTORS BY HYDROXYL RADICALS IN RAT CORTICAL-NEURONS IN-VITRO

Oxygen-derived reactive species generated by xanthine/xanthine oxidase (X/XO) can modulate the N-methyl-D-aspartate (NMDA) receptor via its redox-sensitive site. Here it is shown that hydroxyl radicals are the agents responsible for NMDA receptor oxidation by X/XO. Spectrophotome tric assays revealed that the amounts of superoxide anion and H2O2 pro duced by X/XO were not decreased by the hydroxyl radical-specific scav enger mannitol. This sugar, however, could prevent most of the oxidizi ng actions of NMDA receptors by X/XO, but not by the thiol oxidizing a gent 5,5'-dithio-bis-nitrobenzoic acid. Finally, a non-enzymatic sourc e of hydroxyl radicals was also effective in oxidizing the receptor's redox site. Hydroxyl radicals may thus represent the final common path way for the modulation of NMDA receptor function by oxygen-derived fre e radical generating systems.