Effects of ethanol on muscarinic receptor-stimulated c-fos expression in human neuroblastoma cells.
The effect of ethanol exposure on muscarinic receptor-stimulated expression of c-fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced carbachol-stimulated c-fos mRNA expression, analyzed with Northern blot, and Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre-incubation with muscarinic antagonists or the protein kinase C inhibitor GF109203X demonstrated that, in both control and ethanol-treated cells, carbachol-induced c-fos expression was mediated via muscarinic M1 receptors and to a large extent through protein kinase C. However, phorbol ester-induced c-fos expression was unaffected in ethanol-treated cells. Acute exposure to ethanol caused a suppression of both carbachol- and phorbol ester-stimulated c-fos expression. These results demonstrate that muscarinic receptor-stimulated gene expression is sensitive to both acute and long-term ethanol exposure.
Ding
W Q
WQ
Department of Medical Neurochemistry, Lund University Hospital, Sweden.
Larsson
C
C
Simonsson
P
P
Alling
C
C
D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018721:Muscarinic Agonists; D010703:Phorbol Esters; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D018808:Transcription Factor AP-1; D000431:Ethanol; D002217:Carbachol; D011493:Protein Kinase C