Evans D M, Richardson P J, Fine A, Mason W T, Oliver Dolly J
Department of Biochemistry, Imperial College, London SW7 2AY, U.K.
Neurochem Int. 1988;13(1):25-36. doi: 10.1016/0197-0186(88)90099-x.
Localization in rat CNS of the acceptors for botulinum neurotoxin (types A and B) was examined by lesioning of cholinergic input to the cortex and immuno-affinity purification of cholinergic nerve terminals. Ibotenic acid lesions of the cortical cholinergic tract caused a small reduction in the content of high affinity binding sites for type A neurotoxin and a concomitant decrease in the activities of acetylcholinesterase and choline acetyltransferase. No such change was observed in the level of acceptors for BoNT B or the extent of immuno-labelling of Chol-I, a cholinergic ganglioside. Purification of cholinergic nerve terminals, using anti-(Chol-I) antibodies gave an equivalent enrichment in the acceptors (high and low affinity) for both toxin types and choline acetyltransferase. Neurotoxin type B (but not type A) inhibited binding of anti-(Chol-I) antibodies to this cholinergic ganglioside on nerve terminals and to semi-purified Chol-I. It can be deduced from these collective findings that the high affinity binding sites for BoNT A and possibly B are localized on cholinergic nerve terminals in the CNS and that the Chol-I ganglioside may be associated with the acceptor for type B toxin.
通过破坏皮质的胆碱能输入以及对胆碱能神经末梢进行免疫亲和纯化,研究了肉毒杆菌神经毒素(A 型和 B 型)受体在大鼠中枢神经系统中的定位。皮质胆碱能束的鹅膏蕈氨酸损伤导致 A 型神经毒素高亲和力结合位点的含量略有降低,同时乙酰胆碱酯酶和胆碱乙酰转移酶的活性也随之下降。在 BoNT B 的受体水平或胆碱能神经节苷脂 Chol-I 的免疫标记程度上未观察到此类变化。使用抗(Chol-I)抗体纯化胆碱能神经末梢,两种毒素类型的受体(高亲和力和低亲和力)以及胆碱乙酰转移酶均得到了同等程度的富集。B 型神经毒素(而非 A 型)抑制抗(Chol-I)抗体与神经末梢上的这种胆碱能神经节苷脂以及半纯化的 Chol-I 的结合。从这些综合研究结果可以推断,BoNT A 以及可能的 B 的高亲和力结合位点位于中枢神经系统的胆碱能神经末梢上,并且 Chol-I 神经节苷脂可能与 B 型毒素的受体相关。