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 quinone (PQQ; 50 μM) regulates N-methyl-d-aspartate (NMDA; 10 μM) receptor activity primarily by reversing the increase in the frequency of openings of the receptor-associated ion channel after chemical reduction with dithiothreitol (DTT; 1 mM). Similar to other redox-active agents, PQQ (50–200 μM) had no effect on the single-channel conductance or arithmetic mean open time of NMDA-activated events. In other experiments, we observed that inhibitory effects of PQQ (50 μM) on NMDA (30 μM)-induced whole-cell responses could be abolished by prior N-ethylmaleimide (500 μM) alkylation of the putative thiol residues that likely comprise the redox site of the receptor. These results demonstrate that PQQ modulates the NMDA receptor by directly oxidizing its redox modulatory site.