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

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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 non-competitive manner. NFA produced a leftward shift in reversal potential (E_rev) 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]