EFFECTS OF ETHANOL ON MUSCARINIC RECEPTOR-STIMULATED C-FOS EXPRESSIONIN HUMAN NEUROBLASTOMA-CELLS

The effect of ethanol exposure on muscarinic receptor-stimulated expre ssion of c-fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced carbachol-stimulated c-fos mRNA expression, analyze d with Northern blot, and Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre-incubation with muscarinic antagonist s or the protein kinase C inhibitor GF109203X demonstrated that, in bo th control and ethanol-treated cells, carbachol-induced c-fos expressi on was mediated via muscarinic M1 receptors and to a large extent thro ugh protein kinase C. However, phorbol ester-induced c-fos expression was unaffected in ethanol-treated cells. Acute exposure to ethanol cau sed a suppression of both carbachol- and phorbol ester-stimulated c-fo s expression. These results demonstrate that muscarinic receptor-stimu lated gene expression is sensitive to both acute and long-term ethanol exposure.