ArticlePLoS pathogens2014
Investigation of acetylcholine receptor diversity in a nematode parasite leads to characterization of tribendimidine- and derquantel-sensitive nAChRs.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 58 citations in OpenAlex.
- A novel anaerobic cholinergic signaling compound, β-alanine betaine, and nAChRs in Ascaris.PLoS neglected tropical diseases · 2026Article
- β-alanine betaine and nAChRs inbioRxiv : the preprint server for biology · 2026Article
- The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisole.PLoS pathogens · 2024Article
- Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model.BMC genomics · 2022Article
- Unified total synthesis of the brevianamide alkaloids enabled by chemical investigations into their biosynthesis.Chemical science · 2022Article
- Electrophysiological Properties of Ion Channels in Ascaris suum Tissue Incorporated into Planar Lipid Bilayers.The Korean journal of parasitology · 2021Article
- Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor fromPharmaceuticals (Basel, Switzerland) · 2021Article
- Anthelmintic resistance and homeostatic plasticity (Brugia malayi).Scientific reports · 2021Article
- Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole.International journal for parasitology. Drugs and drug resistance · 2020Article
- Total synthesis of brevianamide A.Nature chemistry · 2020Article
- EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor.PLoS pathogens · 2020Article
- A Functional Comparison of Homopentameric Nicotinic Acetylcholine Receptors (ACR-16) Receptors FromFrontiers in molecular neuroscience · 2020Article
- Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors.International journal for parasitology. Drugs and drug resistance · 2019Article
- Comparative genomics of the major parasitic worms.Nature genetics · 2019Article
- Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes.International journal for parasitology. Drugs and drug resistance · 2018Article
- Article
- Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum.International journal for parasitology. Drugs and drug resistance · 2018Article
- Acetylcholinesterase and Nicotinic Acetylcholine Receptors in Schistosomes and Other Parasitic Helminths.Molecules (Basel, Switzerland) · 2017Review
- Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta.PLoS genetics · 2017Article
- A BRIEF REVIEW ON THE MODE OF ACTION OF ANTINEMATODAL DRUGS.Acta veterinaria · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Nicotinic acetylcholine receptors (nAChRs) of parasitic nematodes are required for body movement and are targets of important "classical" anthelmintics like levamisole and pyrantel, as well as "novel" anthelmintics like tribendimidine and derquantel. Four biophysical subtypes of nAChR have been observed electrophysiologically in body muscle of the nematode parasite Oesophagostomum dentatum, but their molecular basis was not understood. Additionally, loss of one of these subtypes (G 35 pS) was found to be associated with levamisole resistance. In the present study, we identified and expressed in Xenopus oocytes, four O. dentatum nAChR subunit genes, Ode-unc-38, Ode-unc-63, Ode-unc-29 and Ode-acr-8, to explore the origin of the receptor diversity. When different combinations of subunits were injected in Xenopus oocytes, we reconstituted and characterized four pharmacologically different types of nAChRs with different sensitivities to the cholinergic anthelmintics. Moreover, we demonstrate that the receptor diversity may be affected by the stoichiometric arrangement of the subunits. We show, for the first time, different combinations of subunits from a parasitic nematode that make up receptors sensitive to tribendimidine and derquantel. In addition, we report that the recombinant levamisole-sensitive receptor made up of Ode-UNC-29, Ode-UNC-63, Ode-UNC-38 and Ode-ACR-8 subunits has the same single-channel conductance, 35 pS and 2.4 ms mean open-time properties, as the levamisole-AChR (G35) subtype previously identified in vivo. These data highlight the flexible arrangements of the receptor subunits and their effects on sensitivity and resistance to the cholinergic anthelmintics; pyrantel, tribendimidine and/or derquantel may still be effective on levamisole-resistant worms.
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