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Actions on mammalian and insect nicotinic acetylcholine receptors of harmonine-containing alkaloid extracts from the harlequin ladybird Harmonia axyridis

Patel, RN; Richards, DP; Duce, IR; Birkett, MA; Sattelle, DB; Mellor, IR; (2020) Actions on mammalian and insect nicotinic acetylcholine receptors of harmonine-containing alkaloid extracts from the harlequin ladybird Harmonia axyridis. Pesticide Biochemistry and Physiology , 166 , Article 104561. 10.1016/j.pestbp.2020.104561. Green open access

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Abstract

The harlequin ladybird, Harmonia axyridis (H. axyridis), possesses a strong chemical defence that has contributed to its invasive success. Ladybird beetle defensive chemicals, secreted in response to stress and also found on the coating of laid eggs, are rich in alkaloids that are thought to be responsible for this beetle's 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, hence we have explored the actions of alkaloids of the ladybird H. axyridis on both mammalian and insect nAChRs. Electrophysiological studies on native and functionally expressed recombinant nAChRs were used to establish whether an alkaloid extract from H. axyridis (HAE) targeted nAChRs and whether any selectivity exists for insect over mammalian receptors of this type. HAE was found to be an inhibitor of all nAChRs tested with the voltage-dependence of inhibition and the effect on ACh EC50 differing between nAChR subtypes. Our finding that an HAE fraction consisting almost entirely of harmonine had a strong inhibitory effect points to this alkaloid as a key component of nAChR inhibitory actions. Comparison of HAE inhibition between the mammalian and insect nAChRs investigated indicates some preference for the insect nAChR supporting the view that investigation of ladybird alkaloids shows promise as a method for identifying natural product leads for future insecticide development.

Type: Article
Title: Actions on mammalian and insect nicotinic acetylcholine receptors of harmonine-containing alkaloid extracts from the harlequin ladybird Harmonia axyridis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pestbp.2020.104561
Publisher version: https://doi.org/10.1016/j.pestbp.2020.104561
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Entomology, Physiology, Nicotinic acetylcholine receptor, Alkaloid, Harmonine, Antagonist, Patch-clamp, Voltage-clamp, INTRAGUILD PREDATION, NATURAL-PRODUCTS, ALPHA-SUBUNIT, ION-CHANNEL, COCCINELLIDAE, COLEOPTERA, MUSCLE, RESISTANCE, BEETLE, PHILANTHOTOXIN-343
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10103990
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