The N-methyl-D-aspartate antagonist MK-801 fails to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium toxicity in vitro.
Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuro-protective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor.
Finiels-Marlier
F
F
Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892.
Marini
A M
AM
Williams
P
P
Paul
S M
SM
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism
D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003513:Cycloheximide; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine