Valproyl-CoA and esterified valproic acid are not found in brains of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered
Valproyl-CoA and esterified valproic acid are not found in brains of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered
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DOI：
10.1023/a:1023267224819
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发表时间：
2003-06-01
影响因子：
4.4
通讯作者：
Rosenberger, TA
中科院分区：
文献类型：
--
作者：
Deutsch, J;Rapoport, SI;Rosenberger, TA
丙戊酸钠和锂用于治疗双相情感障碍。在大鼠中，两者都降低了几种脑磷脂中花生四烯酸的营业额，表明花生四烯酸营业额是这些情绪稳定剂的共同作用目标。然而，这些药物降低大脑中花生四烯酸周转的机制并不相同。锂通过降低85-kDa IVA型胞浆磷脂酶A（2）（cPLA（2））的活性和表达来降低周转率;丙戊酸盐不影响cPLA（2）的活性或表达。为了检测丙戊酸盐是否通过直接酯化成磷脂或通过中断中间CoA代谢改变神经膜顺序，我们测量了对照大鼠和丙戊酸钠长期治疗大鼠脑中的丙戊酸-CoA、酯化丙戊酸盐和短链酰基-CoA。在脑中未发现丙戊酰辅酶A和丙戊酸酯的酯化形式，检测限分别为25和37.5 pmol/g脑（-1）。与对照组相比，丙戊酸盐给药确实导致游离CoA和乙酰CoA的脑浓度降低1.4倍和升高1.5倍。因此，大鼠中慢性丙戊酸盐导致的脑花生四烯酸周转减少与丙戊酸CoA或酯化丙戊酸盐的形成无关，但可能涉及CoA和短链酰基CoA中间代谢的变化。
Sodium valproate and lithium are used to treat bipolar disorder. In rats, both reduce the turnover of arachidonic acid in several brain phospholipids, suggesting that arachidonate turnover is a common target of action of these mood stabilizers. However, the mechanisms by which these drugs reduce arachidonate turnover in brain are not the same. Lithium decreases turnover by reducing the activity and expression of the 85-kDa type IVA cytosolic phospholipase A(2) (cPLA(2)); valproate does not affect cPLA(2) activity or expression. To test whether valproate alters neural membrane order by direct esterification into phospholipid or by interrupting intermediary CoA metabolism, we measured valproyl-CoA, esterified valproate, and short chain acyl-CoAs in brains from control rats and rats treated chronically with sodium valproate. Valproyl-CoA and esterified forms of valproate were not found in brain with detection limits of 25 and 37.5 pmol/g brain(-1), respectively. Valproate treatment did result in a 1.4-fold decrease and 1.5-fold increase in the brain concentrations of free CoA and acetyl-CoA when compared to control. Therefore the reduction of brain arachidonic acid turnover by chronic valproate in rats is not related to the formation of valproyl-CoA or esterified valproate, but may involve changes in the intermediary metabolism of CoA and short chain acyl-CoA.