Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neurons.
This study was performed to examine the neuroprotective action of 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro [2,3-b]quinolin-4-yl)acetoamide (MKC-231), which enhances choline uptake and acetylcholine release in the central nervous system. Glutamate neurotoxicity was assessed with cortical cultures obtained from fetal rats. Exposure of cultures to MKC-231 for 12-24 hr ameliorated glutamate cytotoxicity. MKC-231 reduced cytotoxicity induced by ionomycin, a calcium ionophore, but did not affect the cytotoxicity induced by S-nitrosocysteine, a nitric oxide (NO) donor. These findings suggest that MKC-231 protects against glutamate neurotoxicity by suppressing the NO formation triggered by Ca2+-influx.
Akaike
A
A
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Maeda
T
T
Kaneko
S
S
Tamura
Y
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D002794:Choline / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats
D018697:Nootropic Agents; D011804:Quinolines; D018698:Glutamic Acid; D002794:Choline; C092988:MKC 231