Tetanus toxin and botulinum A toxin inhibit acetylcholine release from but not calcium uptake into brain tissue.
Slices or particles from rat forebrain cortex were preloaded with [3H]choline, and the release of [3H]acetylcholine was evoked with potassium ions in a superfusion system. Release depended on the presence of calcium. 1. Incubation of the preloaded tissue preparation for 2 h with tetanus or botulinum A toxin did not change the [3H]acetylcholine content or the ratio [3H]acetylcholine/[3H]choline. Tetanus toxin diminished, dependent on dose and time, the release of [3H]acetylcholine evoked by 25 mM K+. It was about ten times more potent than botulinum A toxin. The effect of botulinum toxin was due to its neurotoxin content. Raising the potassium concentration partially overcame the inhibition by the toxins. Hemicholinium-3, applied to preloaded slices, left the subsequent [3H]acetylcholine release unchanged. Pretreatment of particles with neuraminidase diminished the content of long-chain gangliosides to the detection limit. Such particles remained fully sensitive to tetanus toxin, and at least partially sensitive to botulinum A toxin. 2. The potassium or sea anemone toxin II stimulated uptake of 45Ca2+ into cortex synaptosomes or particles was not inhibited by either toxin. Both toxins appear to impede the Ca2+-dependent mobilization of an easily releasable acetylcholine pool, without inhibiting the transmembranal calcium fluxes.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D009439:Neuraminidase / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects; D013744:Tetanus Toxin / Q000494:pharmacology*; D014316:Tritium
D013744:Tetanus Toxin; D014316:Tritium; D009439:Neuraminidase; D001905:Botulinum Toxins; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium