STIMULATION OF MUSCARINIC RECEPTORS INDUCES EXPRESSION OF INDIVIDUAL FOS AND JUN GENES THROUGH DIFFERENT TRANSDUCTION PATHWAYS

Citation
Wq. Ding et al., STIMULATION OF MUSCARINIC RECEPTORS INDUCES EXPRESSION OF INDIVIDUAL FOS AND JUN GENES THROUGH DIFFERENT TRANSDUCTION PATHWAYS, Journal of neurochemistry, 70(4), 1998, pp. 1722-1729
Citations number
50
Categorie Soggetti
Biology,Neurosciences
Journal title
ISSN journal
00223042
Volume
70
Issue
4
Year of publication
1998
Pages
1722 - 1729
Database
ISI
SICI code
0022-3042(1998)70:4<1722:SOMRIE>2.0.ZU;2-S
Abstract
The transduction pathways coupling muscarinic receptors to induction o f fos and jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced expression of c-fos, fosB, c-jun, j unB, 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 b y elevating the intracellular Ca2+ concentration with a Ca2+ ionophore . The Ca2+ effect was inhibited by KN-62, suggesting an induction thro ugh 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 similar to 70% but had only minor e ffects on the expression of c-jun and junD. On the other hand, preincu bation with KN-62 attenuated the carbachol-induced increase in c-jun a nd junD expression by 70% but had no effect on c-fos, fosB, and junB m RNA levels, Simultaneous inhibition of both protein kinase C and Ca2+/ calmodulin-dependent kinase II completely abolished the carbachol-stim ulated expression of c-jun and junD, but c-fos, fosB, and junB were st ill expressed to a certain extent under this condition. Comparison of the inhibitory effects of GF109203X and Go 6976 suggests the involveme nt of classical protein kinase C isozymes in muscarinic receptor-stimu lated expression of fos and jun genes. These results demonstrate that the muscarinic receptor-induced expression of individual fos and jun g enes is regulated via different pathways, primarily protein kinase C o r Ca2+/calmodulin-dependent kinase II.