(−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors

A - Papers appearing in refereed journals

Richards, D. P., Patel, R. H., Duce, I. R., Khambay, B. P. S., Birkett, M. A., Pickett, J. A. and Mellor, I. R. 2022. (−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors. Molecules. 27 (20), p. 7074. https://doi.org/10.3390/molecules27207074

AuthorsRichards, D. P., Patel, R. H., Duce, I. R., Khambay, B. P. S., Birkett, M. A., Pickett, J. A. and Mellor, I. R.
Abstract

Ladybird beetles (Coleoptera: Coccinellidae) possess strong chemical defences that are secreted in response to stress and are also found on the coating of eggs, which are rich in alkaloids that are responsible for their toxicity to other species. Recent studies have shown that alkaloids from several species of ladybird beetle can target nicotinic acetylcholine receptors (nAChRs) acting as receptor antagonists. Here, we have explored the actions of (−)-adaline, found in the 2-spot (Adalia bipunctata) and 10-spot (Adalia decempunctata) ladybirds, on both mammalian (α1β1γδ, α7, α4β2, α3β4) and insect nAChRs using patch-clamp of TE671 cells and locust brain neurons natively expressing nAChRs, as well as two-electrode voltage clamp of Xenopus laevis oocytes recombinantly expressing nAChRs. All nAChR subtypes were antagonised by (−)-adaline in a time-dependent, voltage-dependent and non-competitive manner with the lowest IC50s at rat α3β4 (0.10 μM) and locust neuron (1.28 μM) nAChRs, at a holding potential of −75 mV. The data imply that (−)-adaline acts as an open channel blocker of nAChRs.

Keywords (−)-adaline; Voltage clamp; Adalia bipunctata; Adalia decempunctata; Patch clamp; Nicotinic acetylcholine receptor
Year of Publication2022
JournalMolecules
Journal citation27 (20), p. 7074
Digital Object Identifier (DOI)https://doi.org/10.3390/molecules27207074
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeBBSRC Doctoral Training Partnership
Publisher's version
Output statusPublished
Publication dates
Online20 Oct 2022
Publication process dates
Accepted17 Oct 2022
ISSN1420-3049
PublisherMDPI

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