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 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.
Takahashi
Kanako
K
Department of Clinical Pharmacology, Meiji Pharmaceutical University, Japan.
Ishii-Nozawa
Reiko
R
Takeuchi
Kouichi
K
Nakazawa
Ken
K
Sato
Kaoru
K
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D027341:Excitatory Amino Acid Transporter 1; C493394:SLC1A3 protein, human; D004008:Diclofenac; D009544:Niflumic Acid