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梭曼模拟器预处理对骨骼肌的影响:与乙酰胆碱酯酶的直接相互作用。

The effects of pretreatment with soman simulator in the skeletal muscle: direct interactions with acetylcholinesterase.

作者信息

Grubic Z, Brank M, Brzin M

机构信息

Institute of Pathophysiology, School of Medicine, University of Ljubljana, Slovenia.

出版信息

Chem Biol Interact. 1993 Jun;87(1-3):253-7. doi: 10.1016/0009-2797(93)90051-y.

Abstract

Soman simulator PDP is a compound that has a chemical structure identical to soman, except that the fluorine atom is replaced by a methyl group which makes PDP unable to bind covalently to the AChE active center. In rats, late mortality observed after treatment with high doses of soman could be prevented by PDP pretreatment. Such pretreatment has been much less efficient in primates. The effect of PDP in rats has been explained by blocking the deposition of soman in so-called soman depots in which soman is stored intact and subsequently released. In this paper we demonstrate that in the presence of PDP, inhibition of rat muscle AChE by soman is reduced in rat but not in human muscle homogenates. This result suggests that at least part of the beneficial effects of PDP pretreatment in rat might be due to the direct interaction of PDP with AChE resulting in reduced AChE phosphorylation by soman.

摘要

梭曼模拟器PDP是一种化学结构与梭曼相同的化合物,只是氟原子被甲基取代,这使得PDP无法与乙酰胆碱酯酶(AChE)活性中心共价结合。在大鼠中,高剂量梭曼治疗后观察到的晚期死亡率可通过PDP预处理来预防。这种预处理在灵长类动物中的效果要差得多。PDP在大鼠中的作用被解释为阻止梭曼在所谓的梭曼储存库中的沉积,在这些储存库中梭曼被完整储存并随后释放。在本文中,我们证明在PDP存在的情况下,梭曼对大鼠肌肉AChE的抑制作用在大鼠肌肉匀浆中降低,但在人肌肉匀浆中没有降低。这一结果表明,PDP预处理在大鼠中的有益作用至少部分可能是由于PDP与AChE的直接相互作用,导致梭曼对AChE的磷酸化作用降低。

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