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Nicotinic acetylcholine receptors regulate type 1 inositol 1,4,5‐trisphosphate receptor expression via calmodulin kinase IV activation
Author(s) -
Mizuno Koji,
Kurokawa Kazuhiro,
Ohkuma Seitaro
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23518
Subject(s) - mecamylamine , methyllycaconitine , chemistry , signal transduction , nicotine , nicotinic agonist , downregulation and upregulation , microbiology and biotechnology , receptor , acetylcholine receptor , inositol , acetylcholine , nicotinic acetylcholine receptor , calcium in biology , endocrinology , medicine , biology , neuroscience , biochemistry , gene
Type 1 inositol 1,4,5‐trisphosphate receptors (IP 3 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 IP 3 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 IP 3 R‐1 expression. The present study, therefore, seeks to clarify the mechanism bgy which nicotine modifies IP 3 R‐1 expression by using mouse cerebral cortical neurons in primary culture. Nicotine induced dose‐ and time‐dependent upregulation of IP 3 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 IP 3 R‐1 upregulation. These results indicate that nAChR activation by nicotine upregulates IP 3 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. © 2014 Wiley Periodicals, Inc.