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
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.