Mechanism for increase in expression of cerebral diazepam binding inhibitor mRNA by nicotine: involvement of L-type voltage-dependent calcium channels.
We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.
Katsura
M
M
Department of Pharmacology, Kawasaki Medical School, 701-0192, Kurashiki, Japan.
Higo
A
A
Tarumi
C
C
Tsujimura
A
A
Takesue
M
M
Mohri
Y
Y
Shuto
K
K
Ohkuma
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D026261:Diazepam Binding Inhibitor; D003992:Dibucaine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002132:Calcium Radioisotopes; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D013449:Sulfonamides; D020867:omega-Agatoxin IVA; D014316:Tritium; D018738:Hexamethonium; D013779:Tetrodotoxin; C063302:KN 62; C017967:W 7; D009538:Nicotine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020866:omega-Conotoxin GVIA; D008012:Lidocaine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D011342:Procainamide; D003992:Dibucaine