Summary
The effects of tetanus toxin and botulinum A toxin on the uptake and evoked release of various neurotransmitters were studied using particles from rat forebrain, corpus striatum and spinal cord.
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1.
Uptake. Tetanus toxin partially inhibits the uptake of glycine and choline into spinal cord synaptosomes. The effect on glycine uptake becomes statistically significant after a lag period of 60\2-120 min. It is no longer present when the toxin is heated, antitoxin-treated or toxoided. The inhibition by botulinum A toxin of choline uptake into spinal cord synaptosomes is weak but measurable, that of glycine uptake is at the borderline of detection.
The uptake of GABA into forebrain cortex synaptosomes is slightly inhibited by tetanus toxin but hardly by botulinum A toxin. The effects of tetanus toxin and botulinum A toxin on the uptake of noradrenaline into striatal synaptosomes are negligible.
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2.
Release. Tetanus toxin inhibits the potassium (25 mM) evoked release of radioactivity from rat forebrain cortex particles preloaded with labelled neurotransmitters. The sensitivity decreases in the following order: Glycine > GABA \2> acetylcholine. The toxin also inhibits the release of radioactivity from striatal particles preloaded with labelled noradrenaline. It is always 10\2-50 times more potent on spinal cord than on brain particles. The sensitivity of the evoked release from the spinal cord decreases in the order glycine > GABA > acetylcholine > noradrenaline.
The toxin is identical with the causative agent because toxin-antitoxin complexes, toxoid and heated toxin do not influence the release from particles preloaded with glycine (spinal cord), GABA (forebrain) and noradrenaline (striatum).
Botulinum toxin resembles tetanus toxin by its ability to diminish the release of radioactivity from preloaded forebrain (acetylcholine > GABA), striatal (noradrenaline), or spinal cord (glycine) particles. The botulinum toxin effect on the striatum (noradrenaline) and on the spinal cord (glycine) is due to its neurotoxin content.
The identity of the toxin and the causative agent has been established by preheating and preincubation with antitoxin.
It is proposed that a) tetanus and, however to a much lesser degree, botulinum A toxin act in a basically similar manner on a process underlying the function of synapses in general, and b) the pronounced sensitivity of glycine and GABA release from spinal cord, together with the axonal ascent of tetanus toxin, may be crucial in the pathogenesis of tetanus.
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The essentials of this communication, which is part of the thesis of 1. Heller, have been presented at the Joint Meeting of the Scandinavian and German Pharmacological Societies, Travemünde 1980 (Bigalke et al. 1980)
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Bigalke, H., Heller, I., Bizzini, B. et al. Tetanus toxin and botulinum A toxin inhibit release and uptake of various transmitters, as studied with particulate preparations from rat brain and spinal cord. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 244–251 (1981). https://doi.org/10.1007/BF00505657
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DOI: https://doi.org/10.1007/BF00505657