ArticlePLoS pathogens2017
Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Evaluation of NTD-O2, a Ghanaian herbal medicine, for onchocerciasis and animal African trypanosomiasis.BMC complementary medicine and therapies · 2025Article
- Contact exposure to ivermectin induces acute mortality and inhibits parasite development in malaria vectors.Scientific reports · 2025Article
- Article
- UnderstandingPathogens (Basel, Switzerland) · 2024Article
- Mosquitocidal effect of ivermectin-treated nettings and sprayed walls on Anopheles gambiae s.s.Scientific reports · 2024Article
- Lethal and sublethal impacts of membrane-fed ivermectin are concentration dependent in Anopheles coluzzii.Parasites & vectors · 2024Article
- A glutamate-gated chloride channel as the mite-specific target-site of dicofol and other diphenylcarbinol acaricides.Communications biology · 2023Article
- Poultry red mite eradication potential of ivermectin and allicin combination treatment.Veterinary medicine and science · 2023Article
- Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic-Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination.Animals : an open access journal from MDPI · 2023Article
- Nodulisporic acid produces direct activation and positive allosteric modulation of AVR-14B, a glutamate-gated chloride channel from adultProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Pharmacological characterization of novel heteromeric GluCl subtypes from Caenorhabditis elegans and parasitic nematodes.British journal of pharmacology · 2022Article
- Change the channel: CysLoop receptor antagonists from nature.Pest management science · 2021Review
- A Double-Edged Sword-Cardiovascular Concerns of Potential Anti-COVID-19 Drugs.Cardiovascular drugs and therapy · 2021Review
- Ivermectin: An Anthelmintic, an Insecticide, and Much More.Trends in parasitology · 2021Review
- Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Article
- The effects of insecticides on two splice variants of the glutamate-gated chloride channel receptor of the major malaria vector, Anopheles gambiae.British journal of pharmacology · 2020Article
- Current therapeutic applications and pharmacokinetic modulations of ivermectin.Veterinary world · 2019Review
- GluClR-mediated inhibitory postsynaptic currents reveal targets for ivermectin and potential mechanisms of ivermectin resistance.PLoS pathogens · 2019Article
- SAHA (Vorinostat) Corrects Inhibitory Synaptic Deficits Caused by Missense Epilepsy Mutations to the GABAFrontiers in molecular neuroscience · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ivermectin (IVM) is a widely-used anthelmintic that works by binding to and activating glutamate-gated chloride channel receptors (GluClRs) in nematodes. The resulting chloride flux inhibits the pharyngeal muscle cells and motor neurons of nematodes, causing death by paralysis or starvation. IVM resistance is an emerging problem in many pest species, necessitating the development of novel drugs. However, drug optimisation requires a quantitative understanding of GluClR activation and modulation mechanisms. Here we investigated the biophysical properties of homomeric α (avr-14b) GluClRs from the parasitic nematode, H. contortus, in the presence of glutamate and IVM. The receptor proved to be highly responsive to low nanomolar concentrations of both compounds. Analysis of single receptor activations demonstrated that the GluClR oscillates between multiple functional states upon the binding of either ligand. The G36'A mutation in the third transmembrane domain, which was previously thought to hinder access of IVM to its binding site, was found to decrease the duration of active periods and increase receptor desensitisation. On an ensemble macropatch level the mutation gave rise to enhanced current decay and desensitisation rates. Because these responses were common to both glutamate and IVM, and were observed under conditions where agonist binding sites were likely saturated, we infer that G36'A affects the intrinsic properties of the receptor with no specific effect on IVM binding mechanisms. These unexpected results provide new insights into the activation and modulatory mechanisms of the H. contortus GluClRs and provide a mechanistic framework upon which the actions of drugs can be reliably interpreted.
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