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Stimulation of Muscarinic Receptors Induces Expression of Individual fos and jun Genes Through Different Transduction Pathways
Author(s) -
Ding WeiQun,
Larsson Christer,
Alling Christer
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70041722.x
Subject(s) - junb , fosb , protein kinase c , immediate early gene , muscarinic acetylcholine receptor , carbachol , microbiology and biotechnology , signal transduction , chemistry , protein kinase a , biology , endocrinology , kinase , receptor , gene expression , stimulation , biochemistry , gene
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 Ca 2+ concentration with a Ca 2+ ionophore. The Ca 2+ effect was inhibited by KN‐62, suggesting an induction through Ca 2+ /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 ∼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 Ca 2+ /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 Ca 2+ /calmodulin‐dependent kinase II.