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New insights on nematode glutamate-gated chloride channels (GluCls) and mode of action of macrocyclic lactones.

New insights on nematode GluCls and mode of action of macrocyclic lactones.
19 January 2022

Macrocyclic lactones are the most widely used anthelmintic drugs for the treatment of parasitic nematodes both in human and animal health. They are agonists of the nematode glutamate-gated chloride channels (GluCls). GluCls subunit composition and pharmacological properties remain largely unknown in most nematodes. A research team at INRAE Nouzilly looked into GluCl diversity and mode of action of macrocyclic lactones and identified and pharmacologically characterised receptors made of highly conserved GluCl subunits. They reconstituted a total of 14 GluCls and observed that the GLC-2 subunit plays a pivotal role in the composition of heteromeric GluCls in nematodes. They also identified a novel GluCl subtype for which a high concentration of the anthelmintics ivermectin and moxidectin reversibly potentiates glutamateinduced response. The study brings a new vision to the diversity of GluCl subtypes in nematodes and promotes novel drug targets for next generation of anthelmintic compounds development.

Link :

Authors : Lamassiaude N, Courtot E, Corset A, Charvet CL, Neveu C

DOI : 10.1111/bph.15703