Nicergoline enhances glutamate uptake via glutamate transporters in rat cortical synaptosomes.
To elucidate the mechanisms of neuroprotective action of nicergoline, we examined its effect on glutamate transport in rat cortical synaptosomes and cloned glutamate transporters. In synaptosomes, nicergoline enhanced the glutamate uptake at 1-10 microM in standard medium and suppressed the increase of extracellular glutamate by reversed transport in low Na(+) medium. Apparent increase of extracellular glutamate concentration by dihydrokinate, an inhibitor of glial glutamate transporter GLT-1, was antagonized by nicergoline. In Xenopus oocytes expressing mouse neuronal glutamate transporter (mEAAC1), the glutamate-induced inward current was enhanced by nicergoline. These results suggest that nicergoline reduces the extracellular glutamate concentration through its effect on glutamate transporters.
Nishida
Atsushi
A
Discovery and Pharmacology Research Laboratories, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan. bon@tanabe.co.jp
Iwata
Hiroshi
H
Kudo
Yukitsuka
Y
Kobayashi
Tsutomu
T
Matsuoka
Yuzo
Y
Kanai
Yoshikatsu
Y
Endou
Hitoshi
H
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009530:Nicergoline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid; D009530:Nicergoline