Activation of adenylate cyclase results in down-regulation of c-jun mRNA expression in rat C6 glioma cells

To investigate the possible mechanisms involved in forskolin-induced c-jun mRNA decrease in rat C6 glioma cells, we examined effects of a PKA inhibito r (H-89), a L-type Ca2+ channel blocker (nimodipine), a calmodulin activati on inhibitor (calmidazolium chloride) and a Ca2+/calmodulin-dependent prote in kinase II inhibitor (KN-62) on forskolin-induced c-jun mRNA down-regulat ion. H-89 caused a reversal of forskolin-induced c-jun mRNA decrease. Furth ermore, nimodipine, KN-62 and calmidazolium chloride partially blocked fors kolin-induced c-jun mRNA down-regulation. Our results suggest that activati on of adenylate cyclase appears to be involved in a down-regulation of c-ju n mRNA expression through a PKA pathway. In addition, L-type calcium channe ls, calmodulin and Ca2+/calmodulin-dependent protein kinase II may be parti ally involved in c-jun mRNA down-regulation induced by forskolin. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.