Abstract
Endplate preparations of the rat left hemidiaphragm were incubated with [3H]choline to label neuronal transmitter stores. Nerve evoked release of newly-synthesized [3H]acetylcholine was measured in the absence of cholinesterase inhibitors to investigate whether snake venom neurotoxins by blocking presynaptic nicotinic autoreceptors affect evoked transmitter release. Contractions of the indirectly stimulated hemidiaphragm were recorded to characterize the blocking effect of α-neurotoxins at the postsynaptic nicotinic receptors.
Neither the long chain neurotoxins α-cobratoxin (1 μg ml−1) and α-bungarotoxin (5 μg ml−1) nor the short chain neurotoxin erabutoxin-b (0.1, 1 and 10 μgml−1) affected the nerve-evoked release of [3H]acetylcholine. κ-Bungarotoxin (1 and 5 μg ml−1), a toxin preferentially blocking neuronal nicotinic receptors, did also not affect evoked [3H]acetylcholine release, whereas (+)-tubocurarine (1 μM) under identical conditions reduced the release by about 50%. α-Bungarotoxin, α-cobratoxin and erabutoxin-b concentration-dependently (0.01–0.6 μg ml−1)inhibited nerve-evoked contractions of the hemidiaphragm. All neurotoxins except erabutoxin-b enhanced the basal tritium efflux immediately when applied to the endplate preparation or to a non-innervated muscle strip labelled with [3H]choline. This effect was attributed to an enhanced efflux of [3H]phosphorylcholine, whereas the efflux of [3H]choline and [3H]acetylcholine was not affected.
It is concluded that the α-neurotoxins and κ-bungarotoxin do not block presynaptic nicotinic receptors of motor nerves. These nicotinic autoreceptors differ from nicotinic receptors localized at the muscle membrane and at autonomic ganglia.
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Apel, C., Říčný, J., Wagner, G. et al. α-Bungarotoxin, κ-bungarotoxin, α-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm. Naunyn-Schmiedeberg's Arch Pharmacol 352, 646–652 (1995). https://doi.org/10.1007/BF00171324
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DOI: https://doi.org/10.1007/BF00171324