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Functional characterization of the oxantel-sensitive acetylcholine receptor from Trichuris muris

Abstract : 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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Contributor : Claude Charvet <>
Submitted on : Wednesday, July 28, 2021 - 4:37:14 PM
Last modification on : Wednesday, September 1, 2021 - 2:06:15 PM


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Tina Vicky Alstrup Hansen, Richard Grencis, Mohamed Issouf, Cédric Neveu, Claude L. Charvet. Functional characterization of the oxantel-sensitive acetylcholine receptor from Trichuris muris. Pharmaceuticals, MDPI, 2021, 14 (7), 15 p. ⟨10.3390/ph14070698⟩. ⟨hal-03299274⟩



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