title: Stimulation of muscarinic receptors induces expression of individual fos and jun genes through different transduction pathways.
abstract: 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 Gö 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.
authors.affiliation: Department of Medical Neurochemistry, Institute of Laboratory Medicine, Lund University Hospital, Sweden.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Ding
authors.forename: C
authors.initials: C
authors.lastname: Larsson
authors.forename: C
authors.initials: C
authors.lastname: Alling
mesh_terms: D002118:Calcium / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D006801:Humans; D009116:Muscarine / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D014161:Transduction, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D009116:Muscarine; D002217:Carbachol; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium