| Literature DB >> 7894333 |
H Fukuda1, A Nishida, H Saito, M Shimizu, S Yamawaki.
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-beta 1 antibody prevented the imipramine-mediated activation of PLC. However, preincubation with anti-PLC-gamma 1 or anti-PLC-delta 1 did not prevent activation of PLC. These results suggest that imipramine activates PLC-beta 1 directly without receptor or guanine nucleotide binding protein mediation.Entities:
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Year: 1994 PMID： 7894333 DOI： 10.1016/0197-0186(94)90155-4
Source DB: PubMed Journal: Neurochem Int ISSN： 0197-0186 Impact factor: 3.921