Larsson C, Gustavsson L, Simonsson P, Bergman O, Alling C
Department of Psychiatry and Neurochemistry, Lund University, Sweden.
Eur J Pharmacol. 1994 Jun 15;268(1):19-28. doi: 10.1016/0922-4106(94)90116-3.
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.
在本研究中，对将卡巴胆碱刺激转化为SH-SY5Y神经母细胞瘤细胞中c-fos表达的信号级联进行了研究。1,2-二酰甘油的形成和c-fos表达是通过毒蕈碱型M1受体的刺激介导的，受体刺激的前5分钟对这些事件至关重要。应用1,2-二辛酰甘油可诱导c-fos表达，并且该表达以及卡巴胆碱刺激的c-fos表达均被蛋白激酶C抑制剂抑制。细胞内Ca2+浓度的增加对c-fos表达的影响很小。最大程度的c-fos表达和1,2-二酰甘油形成依赖于细胞外Ca2+。应用蛋白磷酸酶抑制剂冈田酸可增强卡巴胆碱刺激的c-fos表达。这些结果证明了1,2-二酰甘油形成对于毒蕈碱受体刺激的、蛋白激酶C介导的SH-SY5Y细胞中c-fos表达的重要性，并且该级联被冈田酸敏感的蛋白磷酸酶抵消。
