Department of Pharmacology, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
Toxicon. 2013 Aug;70:86-9. doi: 10.1016/j.toxicon.2013.04.016. Epub 2013 May 3.
Snake venom neurotoxins with phospholipase A₂ affect the neuromuscular junction with three distinct phases. There is a transient decrease in twitch height, followed by a facilitatory phase and finally a progressive blockade. It has been suggested that the initial phase is a direct consequence of the binding of the toxins to nerve terminals. This study was designed to determine whether the initial phase is present under conditions that would reduce the enzyme activity of the toxins. At 27 °C, β-bungarotoxin and taipoxin exhibited all three phases, i.e. 5-6 min after exposure to the preparation, twitch height was significantly reduced (P < 0.5) to 50 ± 4% and 64 ± 9% of control respectively. This was followed by facilitation and subsequent blockade. However, at 20 °C, neither toxin exhibited the first phase while the second phase, although reduced, clearly occurred and the blocking activity of these toxins always appeared. The data clearly demonstrate that the initial fall is temperature dependent as reducing the temperature from 27 °C to 20 °C blocks the first phase. As the second phase still occurs the toxins must have bound to their target. Therefore, the first phase cannot simply be a toxin binding step.
蛇毒神经毒素与磷脂酶 A₂ 会影响神经肌肉接头,其过程分为三个不同阶段。首先会出现短暂的肌肉抽搐高度降低,接着是易化阶段,最后是进行性阻滞。有人认为,最初阶段是毒素与神经末梢结合的直接后果。本研究旨在确定在降低毒素酶活性的条件下,是否存在初始阶段。在 27°C 下,β-银环蛇毒素和 taipoxin 均表现出所有三个阶段,即在接触制剂 5-6 分钟后,肌肉抽搐高度分别显著降低(P<0.05)至对照的 50±4%和 64±9%。接着是易化和随后的阻滞。然而,在 20°C 下,两种毒素均未表现出第一阶段,尽管第二阶段虽然减弱,但仍明显发生,这些毒素的阻滞活性始终存在。数据清楚地表明,初始下降是温度依赖性的,因为将温度从 27°C 降低到 20°C 会阻断第一阶段。由于第二阶段仍然发生,毒素必须已经与目标结合。因此,第一阶段不能简单地是毒素结合步骤。