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Chronic Imipramine Administration Amplifies the Serotonin 2A Receptor‐Induced Intracellular Ca 2+ Mobilization in C6 Glioma Cells Through a Calmodulin‐Dependent Pathway
Author(s) -
Muraoka Shinichiro,
Kamei Kenji,
Muneoka Katsumasa,
Takigawa Morikuni
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71041709.x
Subject(s) - imipramine , intracellular , glioma , serotonin , calmodulin , mobilization , chemistry , receptor , calcium in biology , endocrinology , microbiology and biotechnology , biophysics , medicine , calcium , pharmacology , biology , biochemistry , cancer research , pathology , political science , alternative medicine , law
In the present study, we examined whether chronic exposure of C6BU‐1 cells to 100 n M of several different types of antidepressants directly influences serotonin 2A (5‐HT 2A ) receptor‐stimulated intracellular Ca 2+ mobilization. Imipramine, desipramine, clomipramine, and maprotiline amplified the 5‐HT response at 48, but not at 2, h. Imipramine increased the maximum response to 5‐HT without altering the EC 50 of the dose‐response curve. This effect was time dependent and cycloheximide blocked the maximal induction, suggesting an essential role for protein synthesis in this process. Previous exposure of the cells to thrombin or isoproterenol did not influence 5‐HT 2A receptor function and pretreatment with imipramine did not alter the thrombin‐ or bradykinin‐induced Ca 2+ mobilization, which indicates that the effects of imipramine appear to be specific to the 5‐HT 2A receptor. The effect of imipramine was potently suppressed by a calmodulin antagonist, W‐13, in a dose‐dependent manner. Furthermore, this amplified 5‐HT response was blocked by KN‐93, but not by H‐7. Taken together, these results suggest that imipramine has a modulatory effect on the 5‐HT 2A receptor‐coupled intracellular Ca 2+ in C6 cells through a calmodulin‐dependent pathway, possibly involving Ca 2+ /calmodulin kinase activation.