Title
Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole
Campus Units
Biomedical Sciences, Genetics, Development and Cell Biology
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
2020
Journal or Book Title
International Journal for Parasitology: Drugs and Drug Resistance
DOI
10.1016/j.ijpddr.2020.04.002
Abstract
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, Ascaris suum, using RT-PCR and RNAscope in situ hybridization and detected mRNA of nAChR subunits in the cells. These subunits include components of the putative levamisole receptor in A. suum muscle: Asu-unc-38, Asu-unc-29, Asu-unc-63 and Asu-acr-8. Relative expression of these mRNAs in A. suum intestine was quantified by qPCR. We also looked for and found expression of G protein-linked acetylcholine receptors (Asu-gar-1). 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 A. suum, indicating the activation of intestinal nAChRs rather than G protein-linked acetylcholine receptors (GARs) by levamisole. 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).
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Owner
The Authors
Copyright Date
2020
Language
en
File Format
application/pdf
Recommended Citation
McHugh, Mark; Williams, Paul; Verma, Saurabh; Powell-Coffman, Jo Anne; Robertson, Alan P.; and Martin, Richard J., "Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole" (2020). Genetics, Development and Cell Biology Publications. 245.
https://lib.dr.iastate.edu/gdcb_las_pubs/245
Included in
Cell and Developmental Biology Commons, Chemicals and Drugs Commons, Genetics Commons, Parasitology Commons
Comments
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." International Journal for Parasitology: Drugs and Drug Resistance (2020). doi: 10.1016/j.ijpddr.2020.04.002.