Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test
Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test
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DOI：
10.1016/j.toxicon.2010.10.009
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发表时间：
2011-01-01
期刊：
影响因子：
2.8
通讯作者：
Ginnaga, Akihiro
中科院分区：
文献类型：
--
作者：
Torii, Yasushi;Kiyota, Naotoshi;Ginnaga, Akihiro
A型肉毒毒素被用作某些痉挛性神经障碍的治疗剂。根据产生的神经毒素的氨基酸序列变异性，A型生物体被分为四个亚型（A1至A4）。目前，该毒素的市售制剂属于A1亚型。迄今为止，还没有研究比较不同亚型毒素的生物活性特征。采用小鼠膈神经半侧膈肌收缩试验和大鼠握力试验，比较了A1毒素（LL毒素或神经毒素：NTX）和A2毒素（NTX）的作用。在pH7.4和pH6.8时，A2 NTX对神经肌肉传递的抑制作用分别是A1 LL的1.95和3.73倍。A1 LL、A1 NTX和A2 NTX的给药肢体的50%有效剂量，即导致握力降低50%的剂量，即ED 50，分别计算为0.087、0.060和0.040 U/头。A1 LL、A1 NTX和A2 NTX对侧肢体的这些剂量（即TD 50）分别计算为6.35、7.54和15.62 U/头。此外，注射A2 NTX的大鼠恢复对侧肢体的握力所需的时间为17天，而注射A1 LL的大鼠为35天。结果表明，A_2NTX是一种比A_1毒素更有效的神经肌肉阻滞剂，并提示A_2NTX将为神经系统疾病提供一种首选的治疗药物。(C)2010爱思唯尔有限公司保留所有权利。
Botulinum toxin type A is used as a therapeutic agent for some spastic neurological disorders. Type A organisms have been classified into four subtypes (A1 to A4) based on the amino acid sequence variability of the produced neurotoxin. At present, commercially available preparations of the toxin belong to subtype A1. To date, no study has compared the characteristics of the biological activity of toxins from different subtypes. We compared the efficacy of A1 toxin (LL toxin or neurotoxin: NTX) with that of A2 toxin (NTX) employing the twitch tension assay using the mouse phrenic nerve hemidiaphragm and grip strength test in rats. The inhibitory effects on neuromuscular transmission of A2NTX at pH 7.4 and pH 6.8 were 1.95 and 3.73 times more potent than those of A1LL, respectively. The 50% effective doses for the administered limb, the dose which caused a 50% reduction in grip strength, i.e. ED50, of A1LL, A1NTX, and A2NTX were calculated as 0.087, 0.060, and 0.040 U/head, respectively. These doses for the contralateral limb, i.e. TD50, of A1LL, A1NTX, and A2NTX were calculated as 6.35, 7.54, and 15.62 U/head, respectively. In addition, the time required for A2NTX-injected rats to recover the grip strength of the contralateral limb was 17 days, while that for rats injected with A1LL was 35 days. The results indicated that A2NTX is a more potent neuromuscular blocker than A1 toxins, and suggested that A2NTX will provide a preferentical therapeutic agent for neurological disorders. (C) 2010 Elsevier Ltd. All rights reserved.