Research Summary: A Fungal Metabolite Asperparaline A Strongly and Selectively Blocks Insect Nicotinic Acetylcholine Receptors: The First Report on the Mode of Action

ABSTRACT

Asperparalines produced by Aspergillus japonicus JV-23 induce
paralysis in silkworm (Bombyx mori) larvae, but the target
underlying insect toxicity remains unknown. In the present study, we have
investigated the actions of asperparaline A on ligand-gated ion channels
expressed in cultured larval brain neurons of the silkworm using patch-clamp
electrophysiology. Bath-application of asperparaline A (10 µM) had no
effect on the membrane current, but when delivered for 1 min prior to
co-application with 10 µM acetylcholine (ACh), it blocked completely the
ACh-induced current that was sensitive to mecamylamine, a nicotinic
acetylcholine receptor (nAChR)-selective antaogonist. In contrast, 10 µM
asperparaline A was ineffective on the γ-aminobutyric acid- and
L-glutamate-induced responses of the Bombyx larval neurons. The
fungal alkaloid showed no-use dependency in blocking the ACh-induced response
with distinct affinity for the peak and slowly-desensitizing current amplitudes
of the response to 10 µM ACh in terms of IC50 values of 20.2
and 39.6 nM, respectively. Asperparaline A (100 nM) reduced the maximum neuron
response to ACh with a minimal shift in EC50, suggesting that the
alkaloid is non-competitive with ACh. In contrast to showing marked blocking
action on the insect nAChRs, it exhibited only a weak blocking action on chicken
α3β4, α4β2 and α7 nAChRs expressed in Xenopus
laevis
oocytes, suggesting a high selectivity for insect over
certain vertebrate nAChRs.

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Publisher: Public Library of Science

Date Published: 1-April-2011

Author(s): Hirata K., Kataoka S., Furutani S., Hayashi H., Matsuda K.

Link: https://doi.org/10.1371/journal.pone.0018354

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