Tetanus toxin and botulinum A and C neurotoxins inhibit noradrenaline release from cultured mouse brain.
Primary nerve cell cultures from the brainstem of embryonic mice take up [3H]noradrenaline. Release can be evoked by high K+ or sea anemone toxin II and depends on Ca2+. The cultures allow neurochemical studies on the long-term actions of clostridial neurotoxins. Tetanus and botulinum A and C neurotoxins partially inhibit the absolute and fractional release evoked by high K+, as well as the fractional basal release. The detection limit for the toxins is below 5 pM. Total radioactivity is higher in the poisoned cultures, although the initial velocity of uptake is not measurably influenced by tetanus or botulinum A toxin. Pretreatment with neuraminidase prevents the effects of botulinum A toxin and diminishes those of botulinum C and tetanus toxins. Within 6 days, the cultures partially recover from tetanus toxin poisoning. Antitoxin prevents the actions of the toxin, but only slightly promotes recovery. The data indicate close pharmacological analogies between the clostridial neurotoxins.
Habermann
E
E
Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität, Giessen, F.R.G.
Müller
H
H
Hudel
M
M
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D001933:Brain Stem / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D013744:Tetanus Toxin / Q000494:pharmacology*; D014121:Toxoids / Q000494:pharmacology*
C035415:Clostridium botulinum toxoid; D013744:Tetanus Toxin; D014121:Toxoids; D009439:Neuraminidase; D001905:Botulinum Toxins; D009638:Norepinephrine