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Imipramine stimulates phospholipase C activity in rat brain |
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| Authors: | Hiroyuki Fukuda Akira Nishida Hiroshi Saito Masami Shimizu and Shigeto Yamawaki |
| Institution: | a Department of Psychiatry and Neuroscience, Institute of Clinical Research, Kure National Hospital, 3-1 Aoyama-cho, Kure, Hiroshima 737, Japan b Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Hiroshima, Japan |
| Abstract: | We previously demonstrated that antidepressant drugs (ADs) cause Ca2+ release from inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in cultured neurons of rat frontal cortex. The present study examines the mechanism by which tricyclic ADs activate phospholipase C (PLC) in rat frontal cortex. Using an exogenous substrate to measure PLC activity, we demonstrated that a tricyclic AD, imipramine, stimulated PLC activity of the frontal cortex membrane in a concentration-dependent manner. Two tricyclic ADs, desipramine and amitriptyline, also stimulated PLC activity, while Li+ or pargyline had no effect on PLC activity. Although imipramine did not activate PLC in the membrane in the absence of Ca2+, imipramine synergistically activated PLC in the presence of Ca2+. This result indicates that the mechanism of PLC activation by imipramine is different from its activation by Ca2+. Imipramine stimulated PLC activity in the cytosol of rat frontal cortex as well as in the membrane. Preincubation of the cytosol with anti-PLC-β1 antibody prevented the imipramine-mediated activation of PLC. However, preincubation with anti-PLC-γ1 or anti-PLC-δ1 did not prevent activation of PLC. These results suggest that imipramine activates PLC-β1 directly without receptor or guanine nucleotide binding protein mediation. |
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