Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

被引：118

作者：

Bosetti, F ^{[1
]}

Rintala, J ^{[1
]}

Seemann, R ^{[1
]}

Rosenberger, TA ^{[1
]}

Contreras, MA ^{[1
]}

Rapoport, SI ^{[1
]}

Chang, MC ^{[1
]}

机构：

[1] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR PSYCHIATRY | 2002年 / 7卷 / 08期

关键词：

lithium; arachidonic acid; cyclooxygenase; phospholipase A(2); prostaglandin; brain; rat; chronic; bipolar disorder;

D O I：

10.1038/sj.mp.4001111

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：

Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A(2) (cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E-2 (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca2+ independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

引用

页码：845 / 850

页数：6

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