ALPHA-CONOTOXIN GI PRODUCES TETANIC FADE AT THE RAT NEUROMUSCULAR-JUNCTION
ALPHA-CONOTOXIN GI PRODUCES TETANIC FADE AT THE RAT NEUROMUSCULAR-JUNCTION
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DOI：
10.1016/0041-0101(92)90381-e
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发表时间：
1992-08-01
期刊：
影响因子：
2.8
通讯作者：
MARSHALL, IG
中科院分区：
文献类型：
--
作者：
BLOUNT, K;JOHNSON, A;MARSHALL, IG
已在离体大鼠半横膈制备物中测定了海洋蜗牛毒素α-芋螺毒素GI产生单次诱发抽搐的阻断和产生强直性和四联衰减的能力。结果进行了比较与可逆的（维库）和不可逆的（α-银环蛇毒素）烟碱乙酰胆碱拮抗剂，并已解释后和prejunctional烟碱乙酰胆碱受体在神经肌肉接头的相对影响。α-芋螺毒素GI（0.5-2-μ M）产生浓度依赖性，容易可逆，降低单次抽搐和50 Hz强直的峰值幅度，并增加强直和四列衰减。就所有测量的张力参数而言，α-芋螺毒素GI的效力始终是维库溴铵的2-3倍。α-芋螺毒素GI和维库溴铵在产生强直性消退和阻断强直性收缩方面比阻断单次抽搐的效力高约2倍。与α-芋螺毒素GI和维库溴铵相反，α-银环蛇毒素（0.13 μ M）将单次抽搐和50 Hz强直的峰值幅度降低到相同的程度，而没有出现大程度的强直或四列衰减。基于比较的神经肌肉阻滞的体外时间过程和维库溴铵，α-芋螺毒素GI和α-银环蛇毒素对抽搐，破伤风和四列的相对影响，我们得出结论，α-芋螺毒素GI在神经肌肉接头前和后连接活动。在这方面，α-芋螺毒素GI类似于临床上使用的竞争性神经肌肉阻断药物，而不是不可逆的蛇α-神经毒素。
The ability of the marine snail toxin, alpha-conotoxin GI, to produce blockade of singly evoked twitches and to produce tetanic and train-of-four fade has been determined in the isolated rat hemidiaphragm preparation. Results were compared to those obtained with a reversible (vecuronium) and an irreversible (alpha-bungarotoxin) nicotinic acetylcholine antagonist and have been interpreted in terms of relative effects on post- and prejunctional nicotinic acetylcholine receptors at the neuromuscular junction. Alpha-Conotoxin GI (0.5-2-mu-M) produced a concentration-dependent, readily reversible, decrease in the peak amplitude of single twitches and 50 Hz tetani, and an increase in tetanic and train-of-four fade. Alpha-Conotoxin GI was consistently 2-3-fold more potent than vecuronium with respect to all of the measured tension parameters. Both alpha-conotoxin GI and vecuronium were approximately 2-fold more potent in producing tetanic fade and in blocking tetanic contractions than in blocking single twitches. In contrast to both alpha-conotoxin GI and vecuronium, alpha-bungarotoxin (0.13-mu-M) reduced the peak amplitude of both single twitches and 50 Hz tetani to the same extent without the appearance of a large degree of tetanic or train-of-four fade. Based on a comparison of the in vitro time course of neuromuscular block and of the relative effects of vecuronium, alpha-conotoxin GI and alpha-bungarotoxin on twitches, tetani and trains-of-four, we conclude that alpha-conotoxin GI has both pre- and postjunctional activity at the neuromuscular junction. In this respect, alpha-conotoxin GI resembles the clinically used competitive neuromuscular blocking drugs rather than the irreversible snake alpha-neurotoxins.