title: Niflumic acid activates additional currents of the human glial L-glutamate transporter EAAT1 in a substrate-dependent manner.
abstract: The astrocytic L-glutamate (L-Glu) transporter EAAT1 participates in the removal of L-Glu from the synaptic cleft and maintenance of non-toxic concentrations in the extracellular fluid. We have shown that niflumic acid (NFA), a non-steroidal anti-inflammatory drug (NSAIDs), alters L-Glu-induced EAAT1 currents in a voltage-dependent manner using the two-electrode voltage clamp technique in Xenopus oocytes expressing EAAT1. In this study, we characterised the effects of NFA on each type of ion-flux through EAAT1. NFA modulated currents induced by both L-Glu and L-aspartate (L-Asp) in a voltage-dependent manner. Ion-substitution experiments revealed that the activation of additional H(+) conductance was involved in the modulation of currents induced by L-Asp and L-Glu, but Cl(-) was involved only with the L-Asp currents. NFA activated additional currents of EAAT1 in a substrate-dependent manner.
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences.
authors.forename: Kanako
authors.initials: K
authors.lastname: Takahashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Ishii-Nozawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Ken
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekino
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001224:Aspartic Acid / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009544:Niflumic Acid / Q000494:pharmacology*; D009865:Oocytes; D012964:Sodium / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D027341:Excitatory Amino Acid Transporter 1; C493394:SLC1A3 protein, human; D001224:Aspartic Acid; D018698:Glutamic Acid; D009544:Niflumic Acid; D012964:Sodium