Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor from Trichuris muris

The human whipworm, Trichuris trichiura, is estimated to infect 289.6 million people globally. Control of human trichuriasis is a particular challenge, as most anthelmintics have a limited single-dose efficacy, with the striking exception of the narrow-spectrum anthelmintic, oxantel. We recently ide...

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Published inPharmaceuticals (Basel, Switzerland) Vol. 14; no. 7; p. 698
Main Authors Hansen, Tina V. A., Grencis, Richard K., Issouf, Mohamed, Neveu, Cédric, Charvet, Claude L.
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 20.07.2021
MDPI
Subjects
Amino acids
Animal biology
antiparasitic drugs
Cloning
electrophysiology
helminths
Life Sciences
Ligands
Microbiology and Parasitology
nAChR
Nematodes
oxantel
Parasitology
Trichuris
Veterinary medicine and animal Health
NAChR
xenopus oocytes
oxantel
Electrophysiology
Antiparasitic drugs
Helminths
Trichuris
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Summary:The human whipworm, Trichuris trichiura, is estimated to infect 289.6 million people globally. Control of human trichuriasis is a particular challenge, as most anthelmintics have a limited single-dose efficacy, with the striking exception of the narrow-spectrum anthelmintic, oxantel. We recently identified a novel ACR-16-like subunit from the pig whipworm, T. suis which gave rise to a functional acetylcholine receptor (nAChR) preferentially activated by oxantel. However, there is no ion channel described in the mouse model parasite T. muris so far. Here, we have identified the ACR-16-like and ACR-19 subunits from T. muris, and performed the functional characterization of the receptors in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. We found that the ACR-16-like subunit from T. muris formed a homomeric receptor gated by acetylcholine whereas the ACR-19 failed to create a functional channel. The subsequent pharmacological analysis of the Tmu-ACR-16-like receptor revealed that acetylcholine and oxantel were equally potent. The Tmu-ACR-16-like was more responsive to the toxic agonist epibatidine, but insensitive to pyrantel, in contrast to the Tsu-ACR-16-like receptor. These findings confirm that the ACR-16-like nAChR from Trichuris spp. is a preferential drug target for oxantel, and highlights the pharmacological difference between Trichuris species.
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ISSN:1424-8247
1424-8247
DOI:10.3390/ph14070698