Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1.
Riluzole exerts a neuroprotective effect through different mechanisms, including action on glutamatergic transmission. We investigated whether this drug affects glutamate transporter-mediated uptake, using clonal cell lines stably expressing the rat glutamate transporters GLAST, GLT1 or EAAC1. We found that riluzole significantly increased glutamate uptake in a dose-dependent manner; kinetic analysis indicated that the apparent affinity of glutamate for the transporters was significantly increased, with similar effects in the three cell lines. This may facilitate the buffering of excessive extracellular glutamate under pathological conditions suggesting that riluzole's neuroprotective action might be partly mediated by its activating effect on glutamate uptake.
Fumagalli
Elena
E
Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy. fumagalli@marionegri.it
Funicello
Marcella
M
Rauen
Thomas
T
Gobbi
Marco
M
Mennini
Tiziana
T
D027322:Amino Acid Transport System X-AG / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D027342:Excitatory Amino Acid Transporter 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D019782:Riluzole / Q000494:pharmacology*; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D012694:Serine; C020889:dihydrokainic acid; C036040:serine O-sulfate; D019782:Riluzole; D007608:Kainic Acid