Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole

dc.contributor.author McHugh, Mark
dc.contributor.author Williams, Paul
dc.contributor.author Verma, Saurabh
dc.contributor.author Powell-Coffman, Jo Anne
dc.contributor.author Powell-Coffman, Jo Anne
dc.contributor.author Robertson, Alan
dc.contributor.author Martin, Richard
dc.contributor.department Biomedical Sciences
dc.contributor.department Genetics, Development and Cell Biology
dc.date 2020-05-04T20:51:42.000
dc.date.accessioned 2020-06-30T04:02:14Z
dc.date.available 2020-06-30T04:02:14Z
dc.date.copyright Wed Jan 01 00:00:00 UTC 2020
dc.date.issued 2020-01-01
dc.description.abstract <p>Cholinergic agonists, like levamisole, are a major class of anthelmintic drug that are known to act selectively on nicotinic acetylcholine receptors (nAChRs) on the somatic muscle and nerves of nematode parasites to produce their contraction and spastic paralysis. Previous studies have suggested that in addition to the nAChRs found on muscle and nerves, there are nAChRs on non-excitable tissues of nematode parasites. We looked for evidence of nAChRs expression in the cells of the intestine of the large pig nematode, <em>Ascaris suum,</em> using RT-PCR and RNAscope <em>in situ</em> hybridization and detected mRNA of nAChR subunits in the cells. These subunits include components of the putative levamisole receptor in <em>A. suum</em> muscle: <em>Asu-unc-38, Asu-unc-29, Asu-unc-63 and Asu-acr-8</em>. Relative expression of these mRNAs in <em>A. suum</em> intestine was quantified by qPCR. We also looked for and found expression of G protein-linked acetylcholine receptors (<em>Asu-gar-1</em>). We used Fluo-3 AM to detect intracellular calcium changes in response to receptor activation by acetylcholine (as a non-selective agonist) and levamisole (as an L-type nAChR agonist) to look for evidence of functioning nAChRs in the intestine. We found that both acetylcholine and levamisole elicited increases in intracellular calcium but their signal profiles in isolated intestinal tissues were different, suggesting activation of different receptor sets. The levamisole responses were blocked by mecamylamine, a nicotinic receptor antagonist in <em>A. suum,</em> indicating the activation of intestinal nAChRs rather than G protein-linked acetylcholine receptors (GARs) by levamisole<em>.</em> The detection of nAChRs in cells of the intestine, in addition to those on muscles and nerves, reveals another site of action of the cholinergic anthelmintics and a site that may contribute to the synergistic interactions of cholinergic anthelmintics with other anthelmintics that affect the intestine (Cry5B).</p>
dc.description.comments <p>This is a manuscript of an article published as McHugh, Mark, Paul Williams, Saurabh Verma, Jo Anne Powell-Coffman, Alan P. Robertson, and Richard J. Martin. "Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole." <em>International Journal for Parasitology: Drugs and Drug Resistance</em> (2020). doi: <a href="https://doi.org/10.1016/j.ijpddr.2020.04.002" target="_blank" title="Persistent link using digital object identifier">10.1016/j.ijpddr.2020.04.002</a>.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/gdcb_las_pubs/245/
dc.identifier.articleid 1249
dc.identifier.contextkey 17625312
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath gdcb_las_pubs/245
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/37922
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/gdcb_las_pubs/245/2020_PowellCoffman_CholinergicReceptorsManuscript.pdf|||Fri Jan 14 22:54:01 UTC 2022
dc.source.uri 10.1016/j.ijpddr.2020.04.002
dc.subject.disciplines Cell and Developmental Biology
dc.subject.disciplines Chemicals and Drugs
dc.subject.disciplines Genetics
dc.subject.disciplines Parasitology
dc.subject.keywords Levamisole
dc.subject.keywords Nicotinic acetylcholine receptors
dc.subject.keywords Intestine
dc.subject.keywords Calcium signaling
dc.title Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 4f85b957-cce1-4b97-9e44-4f75199c0b3c
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
relation.isOrgUnitOfPublication 9e603b30-6443-4b8e-aff5-57de4a7e4cb2
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