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Two Non-steroidal Anti-inflammatory Drugs,Niflumic Acid and Diclofenac,Inhibit the Human Glutamate Transporter EAAT1 Through Different Mechanisms
Authors:Kanako Takahashi  Reiko Ishii-Nozawa  Kouichi Takeuchi  Ken Nakazawa  Kaoru Sato
Affiliation:1. Department of Clinical Pharmacology, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose, Tokyo 204-8588, Japan;2. Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
Abstract: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:niflumic acid  diclofenac
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