Functional Characterization of the Oxantel-Sensitive Acetylcholine Receptor from .

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.