Stimulation of muscarinic receptors induces expression of individual fos and jun genes through different transduction pathways

Wei-Qun Ding, Christer Larsson, Christer Alling

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The transduction pathways coupling muscarinic receptors to induction of fos and jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced expression of c-fos, fosB, c-jun, junB, and junD. This effect was abolished by pretreatment with atropine, indicating an involvement of muscarinic receptors. These genes were also induced by activation of protein kinase C with phorbol ester or by elevating the intracellular Ca2+ concentration with a Ca2+ ionophore. The Ca2+ effect was inhibited by KN-62, suggesting an induction through Ca2+/calmodulin-dependent kinase II. Inhibition of protein kinase C with GF109203X suppressed the carbachol-stimulated increase in mRNA levels of c-fos, fosB, and junB by approximately 70% but had only minor effects on the expression of c-jun and junD. On the other hand, preincubation with KN-62 attenuated the carbachol-induced increase in c-jun and junD expression by 70% but had no effect on c-fos, fosB, and junB mRNA levels. Simultaneous inhibition of both protein kinase C and Ca2+/calmodulin-dependent kinase II completely abolished the carbachol-stimulated expression of c-jun and junD, but c-fos, fosB, and junB were still expressed to a certain extent under this condition. Comparison of the inhibitory effects of GF109203X and Go 6976 suggests the involvement of classical protein kinase C isozymes in muscarinic receptor-stimulated expression of fos and jun genes. These results demonstrate that the muscarinic receptor-induced expression of individual fos and jun genes is regulated via different pathways, primarily protein kinase C or Ca2+/calmodulin-dependent kinase II.
Original languageEnglish
Pages (from-to)1722-1729
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - 1998

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Division of Clinical Chemistry and Pharmacology (013250300), Tumour Cell Biology (013017530)

Subject classification (UKÄ)

  • Neurosciences


  • Muscarinic receptor
  • Protein kinase C
  • Immediate-early genes
  • SH-SY5Y neuroblastoma cells
  • Ca2+/calmodulin-dependent kinase II


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