L-DOPA neurotoxicity is mediated by glutamate release in cultured rat striatal neurons.
The exposure of cultured rat striatal neurons to L-DOPA caused marked cell death. The L-DOPA cytotoxicity was inhibited by the addition of Mg2+ to and by the removal of Ca2+ from the culture medium, and also by the application of tetrodotoxin. Moreover, prolonged application of L-DOPA increased the glutamate content in the culture medium. These results indicate that L-DOPA produces neurotoxicity by facilitating glutamate release.
Maeda
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Cheng
N
N
Kume
T
T
Kaneko
S
S
Kouchiyama
H
H
Akaike
A
A
Ueda
M
M
Satoh
M
M
Goshima
Y
Y
Misu
Y
Y
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D003470:Culture Media; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism*; D007980:Levodopa / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D003470:Culture Media; D009498:Neurotoxins; D018698:Glutamic Acid; D013779:Tetrodotoxin; D007980:Levodopa; D008274:Magnesium; D002118:Calcium