Nicergoline Enhances Glutamate Uptake via Glutamate Transporters in Rat Cortical Synaptosomes

Atsushi Nishida; Hiroshi Iwata; Yukitsuka Kudo; Tsutomu Kobayashi; Yuzo Matsuoka; Yoshikatsu Kanai; Hitoshi Endou

doi:10.1248/bpb.27.817

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Nicergoline Enhances Glutamate Uptake via Glutamate Transporters in Rat Cortical Synaptosomes

Atsushi Nishida, Hiroshi Iwata, Yukitsuka Kudo, Tsutomu Kobayashi, Yuzo Matsuoka, Yoshikatsu Kanai, Hitoshi Endou

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Keywords: glutamate transporter, nicergoline, glutamate uptake, glutamate reversed transport, synaptosome, Xenopus oocyte

JOURNAL FREE ACCESS

2004 Volume 27 Issue 6 Pages 817-820

DOI https://doi.org/10.1248/bpb.27.817

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Abstract

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 μM 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.

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