IMIPRAMINE STIMULATES PHOSPHOLIPASE-C ACTIVITY IN RAT-BRAIN

被引：28

作者：

FUKUDA, H ^{[1
]}

NISHIDA, A ^{[1
]}

SAITO, H ^{[1
]}

SHIMIZU, M ^{[1
]}

YAMAWAKI, S ^{[1
]}

机构：

[1] HIROSHIMA UNIV,SCH MED,DEPT PSYCHIAT & NEUROSCI,HIROSHIMA,JAPAN

来源：

NEUROCHEMISTRY INTERNATIONAL | 1994年 / 25卷 / 06期

关键词：

D O I：

10.1016/0197-0186(94)90155-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(i) 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.

引用

页码：567 / 571

页数：5

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