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Article

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

1
INRAE, Université de Tours, ISP, F-37380 Nouzilly, France
2
Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK
3
MayBiotech SARL, 8 Rue de la Gendarmerie, 97620 Bouéni, France
*
Author to whom correspondence should be addressed.
Academic Editor: Marcelo J. Nieto
Pharmaceuticals 2021, 14(7), 698; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070698
Received: 14 June 2021 / Revised: 10 July 2021 / Accepted: 16 July 2021 / Published: 20 July 2021
(This article belongs to the Special Issue Antiparasitics)
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. View Full-Text
Keywords: Trichuris; antiparasitic drugs; oxantel; nAChR; helminths; electrophysiology; Xenopus oocytes Trichuris; antiparasitic drugs; oxantel; nAChR; helminths; electrophysiology; Xenopus oocytes
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MDPI and ACS Style

Hansen, T.V.A.; Grencis, R.K.; Issouf, M.; Neveu, C.; Charvet, C.L. Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor from Trichuris muris. Pharmaceuticals 2021, 14, 698. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070698

AMA Style

Hansen TVA, Grencis RK, Issouf M, Neveu C, Charvet CL. Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor from Trichuris muris. Pharmaceuticals. 2021; 14(7):698. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070698

Chicago/Turabian Style

Hansen, Tina V.A., Richard K. Grencis, Mohamed Issouf, Cédric Neveu, and Claude L. Charvet 2021. "Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor from Trichuris muris" Pharmaceuticals 14, no. 7: 698. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070698

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