N-Methyl-D-aspartate-induced enhancement of activator protein-1 DNA binding activity is blocked by ethanol in cerebellar granule cells.
The effects of ethanol on N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonist-stimulated activator protein-1 (AP-1) DNA binding activity in primary cultures of rat cerebellar granule cells were investigated. The application of intoxicating concentrations of ethanol produced a concentration-dependent inhibition of NMDA-enhanced AP-1 binding with a significant reduction obtained at 50 mM ethanol. The inhibitory actions of ethanol on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-stimulated AP-1 binding were considerably weaker as compared to the effects seen following administration of NMDA. The AMPA-induced enhancement of AP-1 DNA binding activity was demonstrated both in the absence and presence of cyclothiazide, a drug, which is known to block the desensitization of AMPA receptors. Our data suggest that moderate concentrations of ethanol modulate glutamate-induced alterations of gene expression in brain neurons.
Hou
Y N
YN
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Cebers
G
G
Cebere
A
A
Terenius
L
L
Liljequist
S
S
D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D004268:DNA-Binding Proteins; D000431:Ethanol; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid