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

The human whipworm, , 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...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-07, Vol.14 (7), p.698
Main Authors: Hansen, Tina V A, Grencis, Richard K, Issouf, Mohamed, Neveu, Cédric, Charvet, Claude L
Format: Article
Language:English
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
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Summary:The human whipworm, , 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, 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 so far. Here, we have identified the ACR-16-like and ACR-19 subunits from , and performed the functional characterization of the receptors in oocytes using two-electrode voltage-clamp electrophysiology. We found that the ACR-16-like subunit from formed a homomeric receptor gated by acetylcholine whereas the ACR-19 failed to create a functional channel. The subsequent pharmacological analysis of the -ACR-16-like receptor revealed that acetylcholine and oxantel were equally potent. The -ACR-16-like was more responsive to the toxic agonist epibatidine, but insensitive to pyrantel, in contrast to the -ACR-16-like receptor. These findings confirm that the ACR-16-like nAChR from spp. is a preferential drug target for oxantel, and highlights the pharmacological difference between species.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph14070698