Mechanisms of muscarinic receptor-stimulated expression of c-fos in SH-SY5Y cells.
In this study, the signal cascade transducing carbachol stimulation into c-fos expression in SH-SY5Y neuroblastoma cells was investigated. 1,2-Diacylglycerol formation and c-fos expression were mediated via stimulation of muscarinic M1 receptors and the first 5 min of receptor stimulation were critical for these events. Application of 1,2-dioctanoylglycerol induced c-fos expression and this, as well as carbachol-stimulated c-fos expression, was inhibited by protein kinase C inhibitors. Increasing the intracellular Ca2+ concentration had only small effects on c-fos expression. There was a dependency on extracellular Ca2+ for maximal c-fos expression and 1,2-diacylglycerol formation. The carbachol-stimulated c-fos expression was potentiated by application of the protein phosphatase inhibitor okadaic acid. These results demonstrate the importance of 1,2-diacylglycerol formation for muscarinic receptor-stimulated, protein kinase C-mediated c-fos expression in the SH-SY5Y cells and that this cascade is counteracted by an okadaic acid-sensitive protein phosphatase.
Larsson
C
C
Department of Psychiatry and Neurochemistry, Lund University, Sweden.
Gustavsson
L
L
Simonsson
P
P
Bergman
O
O
Alling
C
C
D002217:Carbachol / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics*; D006801:Humans; D009447:Neuroblastoma; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000302:isolation & purification; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
C011439:1,2-diacylglycerol; D004075:Diglycerides; D004988:Ethers, Cyclic; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D019319:Okadaic Acid; D002217:Carbachol; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases