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Characterization of the Inhibitory Action of Botulinum Neurotoxin Type A on the Release of Several Transmitters from Rat Cerebrocortical Synaptosomes
Author(s) -
Ashton Anthony C.,
Dolly J. Oliver
Publication year - 1988
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.1471-4159.1988.tb02482.x
Subject(s) - neurotoxin , acetylcholine , synaptosome , neurotransmitter , chemistry , cholinergic , toxin , dopamine , catecholamine , inhibitory postsynaptic potential , blockade , pharmacology , biophysics , biochemistry , endocrinology , biology , in vitro , receptor
Under optimised conditions for intoxication, botulinum neurotoxin type A was shown to inhibit ∼90% of Ca 2+ ‐dependent K + ‐evoked release of [ 3 H]acetylcholine, [ 3 H]noradrenaline, and [ 3 H]dopamine from rat cerebrocortical synaptosomes; cholinergic terminals were most susceptible. In each case, the dose‐response curve for the neurotoxin was extended, with about 50% of evoked release being inhibited at ∼10 n M whereas 200 n M was required for the maximal blockade. This may suggest some heterogeneity in the release process. The action of the toxin was time and temperature dependent and appeared to involve binding and sequestration steps prior to blockade of release. The neurotoxin failed to exert any effect on synaptosomal integrity or on Ca 2+ ‐independent release of the transmitters tested; it produced only minimal changes in neurotransmitter uptake although small secondary effects were detected with cholinergic terminals. Blockade by the neurotoxin of Ca 2+ ‐dependent resting release of transmitter was apparent; Sr 2+ , Ba 2+ , or high concentrations of Ca 2+ restored the resting release of 3 H‐catecholamine but not [ 3 H]acetylcholine. Interestingly, none of the latter conditions or 4‐aminopyridine could reverse the toxin‐induced blockade of evoked release. This lack of specificity in its action on synaptosomes. and other published findings, lead to the conclusion that toxin‐sensitive component(s) exist in all nerve terminals that are concerned with transmitter release.