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乙基胆碱氮芥吖丙啶离子对鸡视网膜胆碱能细胞的毒性作用。

The toxic effects of ethylcholine mustard aziridinium ion on cholinergic cells in the chicken retina.

作者信息

Millar T J, Ishimoto I, Boelen M, Epstein M L, Johnson C D, Morgan I G

出版信息

J Neurosci. 1987 Feb;7(2):343-56. doi: 10.1523/JNEUROSCI.07-02-00343.1987.

Abstract

The chicken retina has been used to examine the toxicity of a highly reactive chemical analog of choline, ethylcholine mustard aziridinium ion (ECMA). Following a single intravitreal injection, retinas were analyzed biochemically for CAT and AChE activities, and GABA, glycine, and dopamine levels. Retinas were also examined using histofluorescence for dopamine histochemistry, for AChE, and immunohistochemistry with antibodies to CAT, tyrosine hydroxylase, GABA, 5-HT, Leu-enkephalin, and somatostatin. A dose of 50 nmol ECMA caused a prolonged 70% depletion of CAT activity and a 40% depletion of AChE activity. The other biochemical parameters were unchanged. This result corresponds to the morphological finding that 2 populations of cholinergic cells were destroyed and that the AChE activity associated with their terminal arbors was lost. A third population of cholinergic cells, located towards the middle of the inner nuclear layer, was resistant to the toxic effects of ECMA. The other cell types, except for somatostatin-immunoreactive cells and photoreceptors, which showed transient effects, were unaffected. ECMA therefore appears to be a highly specific toxin for cholinergic cells in the retina.

摘要

鸡视网膜已被用于检测胆碱的一种高反应性化学类似物——乙基胆碱氮芥氮丙啶离子(ECMA)的毒性。单次玻璃体内注射后,对视网膜进行生化分析,检测过氧化氢酶(CAT)和乙酰胆碱酯酶(AChE)活性以及γ-氨基丁酸(GABA)、甘氨酸和多巴胺水平。还使用组织荧光法对视网膜进行多巴胺组织化学、AChE检测,以及用抗CAT、酪氨酸羟化酶、GABA、5-羟色胺(5-HT)、亮氨酸脑啡肽和生长抑素的抗体进行免疫组织化学检测。50 nmol的ECMA剂量导致CAT活性长期降低70%,AChE活性降低40%。其他生化参数未发生变化。这一结果与形态学发现相对应,即两群胆碱能细胞被破坏,与其终末分支相关的AChE活性丧失。位于内核层中部的第三群胆碱能细胞对ECMA的毒性作用具有抗性。除生长抑素免疫反应性细胞和光感受器表现出短暂效应外,其他细胞类型均未受影响。因此,ECMA似乎是视网膜中胆碱能细胞的一种高度特异性毒素。

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