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Senecioylcholine in Heterometrus spinifer scorpion venom activates vertebrate nicotinic acetylcholine receptors
Journal article   Open access   Peer reviewed

Senecioylcholine in Heterometrus spinifer scorpion venom activates vertebrate nicotinic acetylcholine receptors

Rosa E. Prahl, Pratik Neupane, Angela A. Salim, Richard J. Lewis, Irina Vetter, Robert J. Capon, Glenn F. King and Volker Herzig
Frontiers in Arachnid Science, Vol.5, pp.1-9
2026
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Published Version Open Access CC BY V4.0

Abstract

choline ester convergent evolution Heterometrus nicotinic acetylcholine receptors scorpion venom senecioylcholine
Introduction: Scorpion venoms are natural sources of neurotoxins that primarily modulate the properties of neuronal ion channels, particularly voltage-gated sodium and potassium channels. However, they also contain a variety of small bioactive molecules that have been largely neglected in the omics era of toxinological research.Methods: In the present study, we employed a high-throughput FLIPR screen of arthropod venoms against nicotinic acetylcholine receptors (nAChRs) expressed in the human SH-SY5Y neuroblastoma cell line.Results: The venom of the Malaysian forest scorpion Heterometrus spinifer (family: Scorpionidae) proved to be an agonist of nAChRs, and the small choline ester senecioylcholine was identified as being responsible for the observed effect. Synthetic senecioylcholine and its isomers tigloylcholine and angeloylcholine were not insecticidal when injected into sheep blowflies.Discussion: Based on previous reports of senecioylcholine being toxic to vertebrates along with the agonistic effect we observed on human nAChRs, we postulate that senecioylcholine in scorpion venom is likely to assist with vertebrate prey capture and defense against vertebrate predators. Since senecioylcholine has only been previously reported in marine gastropods and moths, its presence in scorpion venom seems to represent an unusual case of convergent evolution.

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