N-Methyl- d-aspartate-induced enhancement of activator protein-1 DNA binding activity is blocked by ethanol in cerebellar granule cells

• Published in: European journal of pharmacology 1996-08, Vol.309 (3), p.307-310
• Main Authors: Hou, Yan-Ning, Cebers, Gvido, Cebere, Aleta, Terenius, Lars, Liljequist, Sture
• Format: Article
• Language: English
• Subjects: Alcoholism and acute alcohol poisoning; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole) propionic acid): AP-1 (activator protein-1) DNA binding; Animals; Biological and medical sciences; Cerebellum - drug effects; DNA-Binding Proteins - drug effects; Dose-Response Relationship, Drug; Ethanol; Ethanol - pharmacology; Granule cell, cerebellar; Medical sciences; Medicin och hälsovetenskap; N-Methylaspartate - pharmacology; NMDA ( N-methyl- d-aspartate); Rats; Rats, Sprague-Dawley; Toxicology; Transcription factor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(96)00438-4

The effects of ethanol on N-methyl- d-asparate (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 α-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.