Simpson L L
J Pharmacol Exp Ther. 1984 Apr;229(1):182-7.
A chromatographically homogenous preparation of the binding fragment from tetanus toxin was tested for its ability to antagonize the neuromuscular blocking properties of native tetanus toxin. At a concentration of 1 X 10(-6) M, the binding fragment antagonized the paralytic effects of native toxin (1 X 10(-9) M) on mouse phrenic nerve-hemidiaphragms. The binding fragment of tetanus toxin (1 X 10(-6) M) also was tested for its ability to antagonize types A to G botulinum neurotoxin. The fragment did not produce statistically significant antagonism of types A, B, D, F and G neurotoxins, but it did produce highly significant antagonism of types C and E neurotoxin. A series of experiments involving column chromatography, dialysis and high-performance liquid chromatography confirmed that the binding fragment rather than a contaminant was responsible for antagonism. Experiments with type C neurotoxin showed that antagonism between the binding fragment and the toxin occurred extracellularly at the level of the cell membrane. The fragment did not act directly on the toxin to produce inactivation, but instead competed with the toxin for a binding site on the membrane. The fact that the binding moiety of tetanus toxin and the binding moiety of botulinum toxin compete for a similar membrane site suggests that the molecules have areas of structural homology. Such homologies, if confirmed, would have important therapeutic implications.
对破伤风毒素结合片段的一种色谱纯制剂进行了测试，以检验其拮抗天然破伤风毒素神经肌肉阻断特性的能力。在浓度为1×10⁻⁶ M时，该结合片段可拮抗天然毒素（1×10⁻⁹ M）对小鼠膈神经-半膈肌的麻痹作用。还测试了破伤风毒素结合片段（1×10⁻⁶ M）拮抗A至G型肉毒杆菌神经毒素的能力。该片段对A、B、D、F和G型神经毒素未产生具有统计学意义的拮抗作用，但对C型和E型神经毒素产生了高度显著的拮抗作用。一系列涉及柱色谱、透析和高效液相色谱的实验证实，产生拮抗作用的是结合片段而非污染物。对C型神经毒素的实验表明，结合片段与毒素之间的拮抗作用发生在细胞膜水平的细胞外。该片段并非直接作用于毒素使其失活，而是与毒素竞争膜上的一个结合位点。破伤风毒素的结合部分与肉毒杆菌毒素的结合部分竞争相似膜位点这一事实表明，这些分子具有结构同源区域。如果这些同源性得到证实，将具有重要的治疗意义。
