Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions
Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions
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DOI：
10.1038/sj.bjp.0705010
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发表时间：
2003-01-01
影响因子：
7.3
通讯作者：
Molgó, J
中科院分区：
文献类型：
--
作者：
Minic, J;Chatonnet, A;Molgó, J
1 本研究的目的是评估丁酰胆碱酯酶 (BChE) 抑制对分离的膈半膈制剂的存在及其生理后果，所述膈半膈制剂取自表达乙酰乙酰胆碱酯酶 (ACH) 和 BChE 的正常小鼠，以及仅表达 BChE 的 AChE 敲除小鼠 (AChE(-/-))。 2 组织化学和酶分析显示正常成熟神经肌肉中 AChE 和 BChE 的丰度3 在正常 NMJ 中，通过使用四异丙基焦磷酰胺 (iso-OMPA) 或班布特罗进行低 Ca2+/高 Mg2+ 中等 BChE 抑制，释放量减少，诱发量子释放减少（类似于 50%）。而用 fasciculin-1、加兰他敏 (10, 20 muM) 或新斯的明 (0.1 - 1 muM) 抑制 AChE 会增加 (50 - 80%) 诱发量子释放。加兰他敏 (80 muM)、新斯的明 (3 - 10 muM)、O-乙基S-2-(二异丙氨基)乙基甲基硫代膦酸 (MTP) 或磷酸盐抑制 AChE 和 BChE 可减少诱发递质释放 (20 - 50%)。4 在 AChE(-/-) NMJ 中，iso-OMPA 预处理可减少诱发释放。5毒蕈碱毒素 3 降低了用低浓度新斯的明、加兰他敏或束蛋白 1 处理的 AChE(-/-) 和正常 NMJ 中的诱发释放，但对用 iso-OMPA、班布特罗、MTP 和磷酸盐预处理的正常 NMJ 没有影响。 6 在正常和 AChE(-/-) NMJ 中，用 iso-OMPA 预处理未能影响微型化的时程。终板电位和全尺寸终板电位。7 总体而言。我们的结果表明，AChE 的抑制或缺失会通过涉及毒蕈碱受体 (mAChR) 来增加诱发的量子释放。而 BChE 抑制则通过不涉及 mAChR 的直接或间接机制减少释放。 BChE 显然并不参与限制乙酰胆碱对突触后受体的作用持续时间，而是参与释放过程的突触前调节步骤。
1 The present study was performed to evaluate the presence and the physiological consequences of butyrylcholinesterase (BChE) inhibition on isolated phrenic-hemidiaphragm preparations from normal mice expressing acet acetylcholinesterase (ACH) and BChE, and from AChE-knockout mice (AChE(-/-)) expressing only BChE.2 Histochemical and enzymatic assays revealed abundance of AChE and BChE in normal mature neuromuscular junctions (NMJs).3 In normal NMJs, in which release was reduced by low Ca2+/high Mg2+ medium BChE inhibition with tetraisopropylpyrophosphoramide (iso-OMPA) or bambuterol decreased (similar to 50%) evoked quantal release. while inhibition of AChE with fasciculin-1, galanthamine (10, 20 muM) or neostigmine (0.1 - 1 muM) increased (50 - 80%) evoked quantal release. Inhibition of both AChE and BChE with galanthamine (80 muM), neostigmine (3 - 10 muM), O-ethylS-2-(diisopropylamino)ethyl-methylphosphono-thioate (MTP) or phospholine decreased evoked transmitter release (20 - 50%).4 In AChE(-/-) NMJs, iso-OMPA pre-treatment decreased evoked release.5 Muscarinic toxin-3 decreased evoked release in both AChE(-/-) and normal NMJs treated with low concentrations of neostigmine, galanthamine or fasciculin-1, but had no effect in normal NMJs pretreated with iso-OMPA, bambuterol, MTP and phospholine.6 In normal and AChE(-/-) NMJs pretreatment with iso-OMPA failed to affect the time course of miniature endplate potentials and full-sized endplate potentials.7 Overall. our results suggest that inhibition or absence of AChE increases evoked quantal release by involving muscarinic receptors (mAChRs). while BChE inhibition decreases release through direct or indirect mechanisms not involving mAChRs. BChE apparently is not implicated in limiting the duration of acetylcholine action on postsynaptic receptors, ut is involved in a presynaptic modulatory step of the release process.