Summary
Tetanus toxin and, to a lesser degree, botulinum A toxin partially depress the basal and the potassium evoked outflow of [3H]noradrenaline from preloaded particulate rat forebrain cortex. The effect is due to the toxins and not to any contaminant, as shown by dialysis, heating and antitoxin treatment, and also by replacement of crystalline botulinum A toxin with purified neurotoxin.
Tetanus toxin also depresses the outflow due to sea anemone toxin II, 4-aminopyridine and d-amphetamine.
The effect of the toxins proceeds with time and strongly depends on temperature. Once manifest the tetanus toxin effect is not reversed by antitoxin.
Pretreatment with V. cholerae neuraminidase degrades the long-chain gangliosides quantitatively to GM1. Tetanus toxin, applied subsequently remains fully active.
High concentrations of tetanus toxin and botulinum A neurotoxin promote the outflow of small amounts of tritium within short incubation times.
It is concluded:
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a)
Tetanus toxin is a broad range neurotoxin which acts on processes subsequent to the depolarization step.
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b)
Long-chain gangliosides are only binding sites, but not receptors of tetanus toxin.
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c)
Botulinum A toxin is less potent but resembles tetanus toxin in both promoting and depressing the outflow of noradrenaline.
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The essentials of this manuscript have been presented to the Ft. Detrick Conference on “The Biomedical Aspects of Botulism”, Frederick, MD., March 16–18, 1981
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Habermann, E. Tetanus toxin and botulinum A neurotoxin inhibit and at higher concentrations enhance noradrenaline outflow from particulate brain cortex in batch. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 105–111 (1981). https://doi.org/10.1007/BF00508834
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DOI: https://doi.org/10.1007/BF00508834