ArticleBritish journal of pharmacology2011
Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 107 citations in OpenAlex.
- Multiple anthelmintic resistance in Haemonchus contortus infecting sheep in Gangetic plains of India.Tropical animal health and production · 2026Article
- Phytochemical Study of the Anthelminthic Potential of Guadeloupean Plant Biodiversity.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Two residues determine nicotinic acetylcholine receptor requirement for RIC-3.Protein science : a publication of the Protein Society · 2023Article
- Allele specific PCR for a major marker of levamisole resistance in Haemonchus contortus.International journal for parasitology. Drugs and drug resistance · 2022Article
- Reconstitution of an N-AChR from Brugia malayi, an evolved change in acetylcholine receptor accessory protein requirements in filarial parasites.PLoS pathogens · 2022Article
- Drug efficacy on zoonotic nematodes of the Anisakidae family: new metabolic data.Parasitology · 2022Article
- Pharmacological characterization of novel heteromeric GluCl subtypes from Caenorhabditis elegans and parasitic nematodes.British journal of pharmacology · 2022Article
- Anthelmintic resistance and homeostatic plasticity (Brugia malayi).Scientific reports · 2021Article
- Action of Carvacrol onPharmaceuticals (Basel, Switzerland) · 2021Article
- Complementary Approaches with Free-living and Parasitic Nematodes to Understanding Anthelmintic Resistance.Trends in parasitology · 2021Review
- The molecular targets of ivermectin and lotilaner in the human louse Pediculus humanus humanus: New prospects for the treatment of pediculosis.PLoS pathogens · 2021Article
- Haemonchosis: A Challenging Parasitic Infection of Sheep and Goats.Animals : an open access journal from MDPI · 2021Article
- Caenorhabditis elegans in anthelmintic research - Old model, new perspectives.International journal for parasitology. Drugs and drug resistance · 2020Review
- Nicotinic acetylcholine receptors: Ex-vivo expression of functional, non-hybrid, heteropentameric receptors from a marine arthropod, Lepeophtheirus salmonis.PLoS pathogens · 2020Article
- Isolation and characterization of a novel member of the ACC ligand-gated chloride channel family, Hco-LCG-46, from the parasitic nematode Haemonchus contortus.Molecular and biochemical parasitology · 2020Article
- A Functional Comparison of Homopentameric Nicotinic Acetylcholine Receptors (ACR-16) Receptors FromFrontiers in molecular neuroscience · 2020Article
- Lupin (Lupinus spp.) seeds exert anthelmintic activity associated with their alkaloid content.Scientific reports · 2019Article
- Investigating the function and possible biological role of an acetylcholine-gated chloride channel subunit (ACC-1) from the parasitic nematode Haemonchus contortus.International journal for parasitology. Drugs and drug resistance · 2018Article
- 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
- Molecular and pharmacological characterization of an acetylcholine-gated chloride channel (ACC-2) from the parasitic nematode Haemonchus contortus.International journal for parasitology. Drugs and drug resistance · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe cholinergic agonist levamisole is widely used to treat parasitic nematode infestations. This anthelmintic drug paralyses worms by activating a class of levamisole-sensitive acetylcholine receptors (L-AChRs) expressed in nematode muscle cells. However, levamisole efficacy has been compromised by the emergence of drug-resistant parasites, especially in gastrointestinal nematodes such as Haemonchus contortus. We report here the first functional reconstitution and pharmacological characterization of H. contortus L-AChRs in a heterologous expression system. EXPERIMENTAL APPROACH: In the free-living nematode Caenorhabditis elegans, five AChR subunit and three ancillary protein genes are necessary in vivo and in vitro to synthesize L-AChRs. We have cloned the H. contortus orthologues of these genes and expressed them in Xenopus oocytes. We reconstituted two types of H. contortus L-AChRs with distinct pharmacologies by combining different receptor subunits. KEY
resultsThe Hco-ACR-8 subunit plays a pivotal role in selective sensitivity to levamisole. As observed with C. elegans L-AChRs, expression of H. contortus receptors requires the ancillary proteins Hco-RIC-3, Hco-UNC-50 and Hco-UNC-74. Using this experimental system, we demonstrated that a truncated Hco-UNC-63 L-AChR subunit, which was specifically detected in a levamisole-resistant H. contortus isolate, but not in levamisole-sensitive strains, hampers the normal function of L-AChRs, when co-expressed with its full-length counterpart. CONCLUSIONS AND IMPLICATIONS: We provide the first functional evidence for a putative molecular mechanism involved in levamisole resistance in any parasitic nematode. This expression system will provide a means to analyse molecular polymorphisms associated with drug resistance at the electrophysiological level.
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