Evaluation of ethanol effects on PLC signal transduction pathways using cell lines of neuronal origin.
Human neuroblastoma cells SH-SY5Y and neuroblastoma-glioma cells NG 108-15 have been used as models for the elucidation of the effects of ethanol on receptor-mediated phospholipase C activity, c-fos mRNA expression and protein kinase C activity. Cells were exposed to ethanol (0-200 mM) for varying periods up to seven days. Agonist stimulated events were obtained in NG 108-15 cells with bradykinin and in SH-SY5Y cells with carbachol. Chronic ethanol exposure reduced the agonist-stimulated formation of inositol 1,4,5-trisphosphate in NG 108-15 cells and in SH-SY5Y cells. 100 mM ethanol for seven days increased the membrane bound and cytosolic forms of protein kinase C activity in SH-SY5Y cells. Carbachol (1 mM) induced a maximal c-fos mRNA response after 40 minutes in SH-SY5Y cells, an effect that could be mimicked through protein kinase C stimulation by phorbol esters.
Alling
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C
Department of Psychiatry and Neurochemistry, Lund University, Sweden.
Bergman
O
O
Larsson
C
C
Simonsson
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P
D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D006801:Humans; D006868:Hydrolysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism*
D010716:Phosphatidylinositols; D012333:RNA, Messenger; D000431:Ethanol; D002217:Carbachol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D001920:Bradykinin