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THE EFFECTS OF BOTULINUM TOXIN ON ACETYLCHOLINE METABOLISM IN MOUSE BRAIN SLICES AND SYNAPTOSOMES
Author(s) -
Gundersen Cameron B.,
Howard Bruce D.
Publication year - 1978
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1978.tb00140.x
Subject(s) - acetylcholine , toxin , synaptosome , choline , chemistry , botulinum toxin , cholinergic , biochemistry , efflux , metabolism , clostridium botulinum , pharmacology , biology , endocrinology , in vitro , neuroscience
The effects of Type A botulinum toxin on acetylcholine metabolism were studied using mouse brain slice and synaptosome preparations. Brain slices that had been incubated with the toxin for 2h exhibited a decreased release of acetylcholine into high K + media. Botulinum toxin did not affect acetylcholine efflux from slices in normal K + media. When labeled choline was present during the release incubation, a‘newly‐synthesized’pool of acetylcholine was formed in the tissue. In toxin‐treated slices exposed to high K + , both the production and the release of this‘newly‐synthesized’acetylcholine were depressed. A possible explanation for these actions of botulinum toxin would be via an inhibition of the high affinity uptake of choline. This hypothesis was tested by measuring the high affinity uptake of [ 3 H]choline into synaptosomes prepared from brain slices. Previous exposure of slices to botulinum toxin caused a significant reduction in the accumulation of label by the synaptosomes. These data are discussed in terms of our current understanding of the mechanism of action of botulinum toxin and the toxin's interaction with the mechanisms regulating acetylcholine turnover.