Nicotinic acetylcholine receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via calmodulin kinase IV activation.
Type 1 inositol 1,4,5-trisphosphate receptors (IP3 R-1) are among the important calcium channels regulating intracellular Ca(2+) concentration in the central nervous system. In a previous study, we showed that drugs of abuse, such as cocaine, methamphetamine, and ethanol, induced IP3 R-1 upregulation via the calcium signal transduction pathway in psychological dependence. Although nicotine, a major component in tobacco smoke, participates in psychological and/or physical dependence, it has not yet been clarified how nicotine alters IP3 R-1 expression. The present study, therefore, seeks to clarify the mechanism bgy which nicotine modifies IP3 R-1 expression by using mouse cerebral cortical neurons in primary culture. Nicotine induced dose- and time-dependent upregulation of IP3 R-1 protein following its mRNA increase, and the latter was significantly suppressed by a nonselective nicotinic acetylcholine receptors (nAChR) antagonist, mecamylamine. Both cFos and phosphorylated-cJun (p-cJun) were immediately increased in the nucleus, together with an increase of calmodulin kinase (CaMK) IV but not CaMKII expression after nicotine exposure. A nonselective inhibitor of CaMKs, KN-93, and a calcium chelating regent, BAPTA-AM, completely suppressed the expression of cFos and p-cJun in the nucleus as well as the nicotine-induced IP3 R-1 upregulation. These results indicate that nAChR activation by nicotine upregulates IP3 R-1 via increase of activator protein-1, which is a cFos and cJun dimmer, in the nucleus, with activation of Ca(2+) signaling transduction processes.
['Mizuno|Koji|K|', 'Kurokawa|Kazuhiro|K|', 'Ohkuma|Seitaro|S|']
D000818:Animals D001596:Benzylamines D002118:Calcium D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 D002478:Cells, Cultured D002540:Cerebral Cortex D002614:Chelating Agents D004533:Egtazic Acid D053496:Inositol 1,4,5-Trisphosphate Receptors D051379:Mice D009474:Neurons D047428:Protein Kinase Inhibitors D016760:Proto-Oncogene Proteins c-fos D016755:Proto-Oncogene Proteins c-jun D012333:RNA, Messenger D011978:Receptors, Nicotinic D013449:Sulfonamides D013997:Time Factors D015854:Up-Regulation
nicotinic acetylcholine receptors type 1 inositol 1,4,5-trisphosphate receptors calcium AP-1