Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain
Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain
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DOI：
10.1038/sj.mp.4001111
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发表时间：
2002-01-01
影响因子：
11
通讯作者：
Chang, MC
中科院分区：
文献类型：
--
作者：
Bosetti, F;Rintala, J;Chang, MC
据报道，大鼠接受氯化锂治疗6周后，脑磷脂中花生四烯酸（AA）的周转减少，AA选择性胞质磷脂酶A（cPLA(2)）的mRNA和蛋白质水平以及酶活性下降(2)。我们现在报道，长期锂给药可以显著降低大鼠脑蛋白水平和环氧化酶-2 （COX-2）的酶活性，但不影响COX-2 mRNA。锂还降低了前列腺素E-2 （PGE(2)）的脑浓度，PGE(2)是AA通过COX反应形成的生物活性产物。COX-1和不依赖Ca2+的iPLA(2) （VI型）不受锂的影响。这些和先前的结果表明，锂靶向涉及cPLA(2)和COX-2的AA级联的一部分。这种效应可能有助于锂在双相情感障碍中的治疗作用。
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.