{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:19:45Z","timestamp":1788578385743,"version":"build-2803163510"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["210349"],"award-info":[{"award-number":["210349"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Effective control of hookworm infections in humans and animals relies on using a small group of anthelmintics. Many of these drugs target cholinergic ligand-gated ion channels, yet the direct activity of anthelmintics has only been studied in a subset of these receptors, primarily in the non-parasitic nematode,<jats:italic>Caenorhabditis elegans<\/jats:italic>. Here we report the characterization of a homopentameric ionotropic acetylcholine receptor (AChR), ACR-16, from<jats:italic>Necator americanus<\/jats:italic>and<jats:italic>Ancylostoma ceylanicum<\/jats:italic>, the first known characterization of human hookworm ion channels. We used two-electrode voltage clamp electrophysiology in<jats:italic>Xenopus laevis<\/jats:italic>oocytes to determine the pharmacodynamics of cholinergics and anthelmintics on ACR-16 from both species of hookworm. The<jats:italic>A. ceylanicum<\/jats:italic>receptor (Ace-ACR-16) was more sensitive to acetylcholine (EC<jats:sub>50<\/jats:sub>= 20.64 \u00b1 0.32 \u03bcM) and nicotine (EC<jats:sub>50<\/jats:sub>= 24.37 \u00b1 2.89 \u03bcM) than the<jats:italic>N. americanus<\/jats:italic>receptor (Nam-ACR-16) (acetylcholine EC<jats:sub>50<\/jats:sub>= 170.1 \u00b1 19.23 \u03bcM; nicotine EC<jats:sub>50<\/jats:sub>= 597.9 \u00b1 59.12 \u03bcM), at which nicotine was a weak partial agonist (% maximal acetylcholine response = 30.4 \u00b1 7.4%). Both receptors were inhibited by 500 \u03bcM levamisole (Ace-ACR-16 = 65.1 \u00b1 14.3% inhibition, Nam-ACR-16 = 79.5 \u00b1 7.7% inhibition), and responded to pyrantel, but only Ace-ACR-16 responded to oxantel. We used<jats:italic>in silico<\/jats:italic>homology modeling to investigate potential structural differences that account for the differences in agonist binding and identified a loop E isoleucine 130 of Nam-ACR-16 as possibly playing a role in oxantel insensitivity. These data indicate that key functional differences exist among ACR-16 receptors from closely related species and suggest mechanisms for differential drug sensitivity.<\/jats:p>","DOI":"10.3389\/fnmol.2020.601102","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T04:24:32Z","timestamp":1606364672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A Functional Comparison of Homopentameric Nicotinic Acetylcholine Receptors (ACR-16) Receptors From Necator americanus and Ancylostoma ceylanicum"],"prefix":"10.3389","volume":"13","author":[{"given":"Mark D.","family":"Kaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Geary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin N.","family":"Beech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1111\/bph.13524","article-title":"Pharmacological profile of Ascaris suum ACR-16, a new homomeric nicotinic acetylcholine receptor widely distributed in Ascaris tissues.","volume":"173","author":"Abongwa","year":"2016","journal-title":"Br. 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