title: Two non-steroidal anti-inflammatory drugs, niflumic acid and diclofenac, inhibit the human glutamate transporter EAAT1 through different mechanisms.
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 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.
authors.affiliation: Department of Clinical Pharmacology, Meiji Pharmaceutical University, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Takahashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Ishii-Nozawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Ken
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D004008:Diclofenac / Q000009:adverse effects / Q000494:pharmacology*; D027341:Excitatory Amino Acid Transporter 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D009544:Niflumic Acid / Q000009:adverse effects / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D027341:Excitatory Amino Acid Transporter 1; C493394:SLC1A3 protein, human; D004008:Diclofenac; D009544:Niflumic Acid