FURTHER EVIDENCE THAT PYRROLOQUINOLINE QUINONE INTERACTS WITH THE N-METHYL-D-ASPARTATE RECEPTOR REDOX SITE IN RAT CORTICAL-NEURONS IN-VITRO

In this study, we show that the essential nutrient pyrroloquinoline qu inone (PQQ; 50 mu M) regulates N-methyl-D-aspartate (NMDA; 10 mu M) re ceptor activity primarily by reversing the increase in the frequency o f openings of the receptor-associated ion channel after chemical reduc tion with dithiothreitol (DTT; 1 mM). Similar to other redox-active ag ents, PQQ (50-200 mu M) had no effect on the single-channel conductanc e or arithmetic mean open time of NMDA-activated events. In other expe riments, we observed that inhibitory effects of PQQ (50 mu M) on NMDA (30 mu M)-induced whole-cell responses could be abolished by prior N-e thylmaleimide (500 mu M) alkylation of the putative thiol residues tha t likely comprise the redox site of the receptor. These results demons trate that PQQ modulates the NMDA receptor by directly oxidizing its r edox modulatory site.