Distinct sites of action of clostridial neurotoxins revealed by double-poisoning of mouse motor nerve terminals.
Distinct sites of action of clostridial neurotoxins revealed by double-poisoning of mouse motor nerve terminals.
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小鼠运动神经末梢双重中毒揭示了梭菌神经毒素的不同作用位点。
DOI：
10.1007/bf00583812
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Dreyer,F
中科院分区：
文献类型：
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作者：
Gansel,M;Penner,R;Dreyer,F
(1)本文研究了破伤风毒素（TeTx）、A型肉毒杆菌神经毒素（BoTx A）和B型肉毒杆菌神经毒素（BoTx B）单、双重中毒对小鼠胸骨三角肌运动终板自发性和神经诱发性量子递质释放的影响。(2)TeTx和BoTx B对自发和神经诱发的递质释放的抑制作用非常相似，除了BoTx B的作用需要低500倍的浓度，并且对温度的依赖性较小。BoTx A对量子释放的抑制作用强于TeTx或BoTx B，但相对而言更容易被4-氨基吡啶（4-AP）所抵消。(3)与BoTx A相反，用TeTx或BoTx B，在50 Hz神经刺激开始后，递质释放的增加延迟了几秒钟，并且量子的突触潜伏期显示出较大的变化。这种释放模式在所有双重中毒实验中也很明显，无论中毒顺序如何。(4)诱发释放的抑制被认为是稍强的TeTx比BoTx B，所以神经诱发的量子释放后，与任何序列的这些毒素的双重中毒的量总是接近TeTx。在任何情况下都没有观察到超累加作用。(5)当除了两种其他毒素中的任一种之外还施加BoTx A时，观察到诱发量子的强烈减少。使用反向中毒序列（BoTx A-TeTx或BoTx A-BoTx B），所得值保持在BoTx A的极低水平。(6)在存在4-AP的情况下，BoTx A和TeTx或BoTx B之间的任何组合的双重中毒（不管中毒顺序如何）显示出超累加效应，因为释放的量子数显著低于单独使用任何毒素（在存在4-AP的情况下）获得的量子数。(7)我们的研究结果表明，破伤风毒素和B型肉毒毒素有一个共同的作用位点，这是不同的，并独立于A型肉毒毒素。
(1) We investigated the effects of single- and double-poisoning with tetanus toxin (TeTx), botulinum neurotoxin type A (BoTx A) and botulinum neurotoxin type B (BoTx B) on spontaneous and nerve-evoked quantal transmitter release at motor endplates of the triangularis sterni preparation of the mouse. (2) Inhibitory effects of TeTx and BoTx B on spontaneous and nerve-evoked transmitter release were very similar, except that the action of BoTx B required 500-fold lower concentrations and was less dependent on temperature. BoTx A caused stronger inhibition of quantal release than TeTx or BoTx B, but was comparatively much easier counteracted by 4-aminopyridine (4-AP). (3) In contrast to BoTx A, with TeTx or BoTx B the increase of transmitter release following onset of 50 Hz nerve stimulation was delayed for a few seconds and synaptic latencies of quanta showed large variations. This release pattern was also evident in all double-poisoning experiments, regardless of intoxication sequence. (4) Inhibition of evoked release was found to be slightly stronger with TeTx than with BoTx B, so the amount of nerve-evoked quanta released after double-poisoning with any sequence of these toxins always approached that of TeTx. In no case supraadditive actions were observed. (5) A strong reduction of evoked quanta was observed when BoTx A was applied in addition to either of the two other toxins. With reversed poisoning sequences (BoTx A-TeTx or BoTx A-BoTx B) the resulting values remained at the extremely low level of BoTx A. (6) In the presence of 4-AP double-poisoning with any combination between BoTx A and TeTx or BoTx B (regardless of intoxication sequence) revealed supra-additive effects, since the number of quanta released was considerably lower than that obtained with any of the toxins alone (in the presence of 4-AP). (7) Our results indicate that tetanus toxin and botulinum toxin type B have a common site of action which is different and independent from that of botulinum toxin type A.