Two Non-steroidal Anti-inflammatory Drugs, Niflumic Acid and Diclofenac, Inhibit the Human Glutamate Transporter EAAT1 Through Different Mechanisms

We investigated the effects of non-steroidal anti-inflammatory drugs on substrate-induced currents of l-glutamate (l-Glu) transporter EAAT1 expressed in Xenopus laevis oocytes. Niflumic acid (NFA) and diclofenac inhibited l-Glu-induced current through EAAT1 in a noncompetitive manner. NFA produced a leftward shift in reversal potential (Erev) of l-Glu-induced current and increased current amplitude at the potentials more negative than −100 mV. Diclofenac had no effects on E rev and inhibited the current amplitude to the same extent at all negative potentials. These results indicate that NFA and diclofenac inhibit the l-Glu-induced EAAT1 current via different mechanisms.[Supplementary methods and Figure: available only at http://dx.doi.org/10.1254/jphs.09260SC] Keywords:: l-glutamate transporter, niflumic acid, diclofenac