Summary
Tetanus toxin and, to a lesser degree, botulinum A toxin inhibit partially and noncompetitively the uptake of [3H]choline into a crude synaptosomal fraction from rat brain cortex. Botulinum toxin acts by its neurotoxin content. The effect is not due to nonspecific synaptosomal damage by the toxins as shown by the lactate dehydrogenase occlusion test, by the absence of swelling and by the preservation of choline stores. The ratio between [3H]acetylcholine and [3H]choline was decreased by both toxins.
Inhibition by either toxin depends strongly on the temperature and duration of incubation, and is preceded by an initial latency period. The effect of tetanus toxin, once manifest, is largely resistant against antitoxin. It is not significantly diminished by pretreatment of the synaptosomes with V. cholerae neuraminidase.
Fixation of 125I-tetanus toxin proceeds fast, is largely independent of temperature and is diminished by pretreatment of the synaptosomes with neuraminidase. Thus only some of the fixation sites, and not the long-chain gangliosides, are required for the effects of tetanus toxin. A slow, temperature-sensitive process links the fixation with the action.
In contrast to rat synaptosomes the chicken preparation is more sensitive to botulinum A than to tetanus toxin, which reflects the differences in sensitivity between live birds and rodents.
Our data underline the similarities between the effects of tetanus and those of botulinum A toxin. Their dependence on time and temperature, the time dependence of efficacy of antitoxin, and the concordance in species specificity indicate that the in vitro system mirros some crucial features of poisoning of isolated organs and live animals.
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Habermann, E., Bigalke, H. & Heller, I. Inhibition of synaptosomal choline uptake by tetanus and botulinum a toxin. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 135–142 (1981). https://doi.org/10.1007/BF00505307
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DOI: https://doi.org/10.1007/BF00505307