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(−)-adaline from the adalia genus of ladybirds is a potent antagonist of insect and specific mammalian nicotinic acetylcholine receptors

Richards, David P., Patel, Rohit N., Duce, Ian R., Khambay, Bhupinder P. S., Birkett, Michael A., Pickett, John A. ORCID: https://orcid.org/0000-0002-1008-6595 and Mellor, Ian R. 2022. (−)-adaline from the adalia genus of ladybirds is a potent antagonist of insect and specific mammalian nicotinic acetylcholine receptors. Molecules 27 (20) , 7074. 10.3390/molecules27207074

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Chemistry
Biosciences
Additional Information: License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher: MDPI
Date of First Compliant Deposit: 17 November 2022
Date of Acceptance: 17 October 2022
Last Modified: 23 Nov 2022 14:56
URI: https://orca.cardiff.ac.uk/id/eprint/154275

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