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Identification et caractérisation fonctionnelle des cibles pharmacologiques des lactones macrocycliques des invertébrés

Abstract : Invertebrates include a wide variety of parasites of human and animal interest. The control of parasites relies on antiparasitic treatment such as macrocyclic lactones (MLs) and isoxazolines. However, emergence of resistant parasites worldwide makes the investigation of the antiparasitic mode of action as well as their pharmacological targets necessary to move forward the actual control strategies. In this context, using a candidate gene approach, we identified the subunits encoding glutamate-gated chloride channels GluCls (avr-14, avr-15, glc-1, glc-2, glc-3, glc-4 and glc-5) in the nematodes Caenorhabditis elegans, Brugia malayi and Parascaris univalens, as well as GluCl and GABA receptors (rdl) of the human body louse Pediculus humanus. The heterologous expression of subunits in xenopus oocytes allowed the identification of new GluCls subtypes and the characterisation of the mode of action of MLs in these three nematodes species. For C. elegans, AVR-14B, GLC-2 and GLC-3 form functional homomeric receptors but not for parasitic nematodes. For the three species, AVR-14B and GLC-2 combine to form receptors sensitive to MLs whereas GLC-2 and GLC-3 only combine for C. elegans and P. univalens. GLC-2/GLC-3 of P. univalens shows original pharmacological properties. For the human louse, toxicity tests demonstrated the pediculicidal effect of MLs and isoxazolines and the expression of ion channel subunits in Xenopus oocytes elucidate their preferential mode of action on GluCl and GABA receptors. The characterisation of these receptors is a first step for the development of new antiparasitic drugs and new control strategies.
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Contributor : Nathalie Katy Chanteloup <>
Submitted on : Wednesday, March 17, 2021 - 3:34:13 PM
Last modification on : Thursday, May 6, 2021 - 2:22:32 PM


Distributed under a Creative Commons Attribution 4.0 International License


  • HAL Id : tel-03172214, version 1



Nicolas Lamassiaude. Identification et caractérisation fonctionnelle des cibles pharmacologiques des lactones macrocycliques des invertébrés. Sciences du Vivant [q-bio]. Université de Tours, 2020. Français. ⟨tel-03172214⟩



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