AN INVESTIGATION OF ACETYLCHOLINESTERASE INHIBITION AND AGING AND CHOLINE-ACETYLTRANSFERASE ACTIVITY FOLLOWING A HIGH-LEVEL ACUTE EXPOSURE TO PARAOXON
AN INVESTIGATION OF ACETYLCHOLINESTERASE INHIBITION AND AGING AND CHOLINE-ACETYLTRANSFERASE ACTIVITY FOLLOWING A HIGH-LEVEL ACUTE EXPOSURE TO PARAOXON
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DOI：
10.1016/0048-3575(89)90003-5
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发表时间：
1989-02-01
影响因子：
4.7
通讯作者：
CHAMBERS, JE
中科院分区：
文献类型：
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作者：
CHAMBERS, HW;CHAMBERS, JE
雄性大鼠被给予高亚致死剂量的有机磷对氧磷（杀虫剂氯磷的强效抗胆碱酯酶代谢物）或用阿托品解毒的致死剂量的对氧磷，以确保存活。这些剂量对脑乙酰胆碱酯酶产生了高水平的持续抑制，在给药2小时内，大脑皮层、纹状体和延髓中的抑制率为83-94%，给药后4天仍为25-45%。延髓的恢复比其他两个脑区快。通过体外暴露于肟再活化剂后剩余的抑制量估计的老化从治疗当天的无老化逐渐增加到治疗后4天的几乎完全老化。虽然胆碱乙酰转移酶活性的变化可能有助于补偿对氧磷诱导的高胆碱能活性，以减少明显的神经行为并使其他行为恢复到正常水平，但在治疗后的任何时间，均未观察到对氧磷或阿托品诱导的大脑皮层或纹状体胆碱乙酰转移酶比活性的变化。
Male rats were given a high sublethal dose of the organophosphate paraoxon (the potent anticholinesterase metabolite of the insecticide parathion) or a lethal dose of paraoxon antidoted with atropine to assure survival. These doses yielded a high level persistent inhibition of brain acetylcholinesterase, with 83-94% inhibition in the cerebral cortex, corpus striatum, and medulla oblongata within 2 hr of treatment, and still 25-45% inhibition 4 days after treatment. Recovery was faster in the medulla oblongata than the other two brain parts. Aging, as estimated by the amount of inhibition remaining after in vitro exposure to an oxime reactivator, gradually increased from no aging on the day of treatment to virtually complete aging at 4 days after treatment. Although a change in choline acetyltransferase activity could have helped compensate for the paraoxon-induced hypercholinergic activity to reduce overt symptomology and return other behaviors to normal levels, no paraoxon- or atropine-induced changes were observed in choline acetyltransferase specific activity in the cerebral cortex or corpus striatum at any time after treatment.