MECHANISMS OF MUSCARINIC RECEPTOR-STIMULATED EXPRESSION OF C-FOS IN SH-SY5Y CELLS

In this study, the signal cascade transducing carbachol stimulation in to c-fos expression in SH-SY5Y neuroblastoma cells was investigated. 1 ,2-Diacylglycerol formation and c-fos expression were mediated via sti mulation of muscarinic M, receptors and the first 5 min of receptor st imulation were critical for these events. Application of 1,2-dioctanoy lglycerol induced c-fos expression and this, as well as carbachol-stim ulated c-fos expression, was inhibited by protein kinase C inhibitors. Increasing the intracellular Ca2+ concentration had only small effect s on c-fos expression. There was a dependency on extracellular Ca2+ fo r maximal c-fos expression and 1,2-diacylglycerol formation. The carba chol-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 recepto r-stimulated, protein kinase C-mediated c-fos expression in the SH-SY5 Y cells and that this cascade is counteracted by an okadaic acid-sensi tive protein phosphatase.