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 inhibitor (H-89), a L-type Ca2+ channel blocker (nimodipine), a calmodulin activation inhibitor (calmidazolium chloride) and a Ca2+/calmodulin-dependent protein kinase II inhibitor (KN-62) on forskolin-induced c-jun mRNA down-regulation. H-89 caused a reversal of forskolin-induced c-jun mRNA decrease. Furthermore, nimodipine, KN-62 and calmidazolium chloride partially blocked forskolin-induced c-jun mRNA down-regulation. Our results suggest that activation of adenylate cyclase appears to be involved in a down-regulation of c-jun mRNA expression through a PKA pathway. In addition, L-type calcium channels, calmodulin and Ca2+/calmodulin-dependent protein kinase II may be partially involved in c-jun mRNA down-regulation induced by forskolin.
Lee
J K
JK
Department of Pharmacology, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
Choi
M R
MR
Song
D K
DK
Huh
S O
SO
Kim
Y H
YH
Suh
H W
HW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007546:Isoquinolines; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D013449:Sulfonamides; D005576:Colforsin; C031938:calmidazolium; D009553:Nimodipine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide