Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole.
Calcium signaling
Intestine
Levamisole
Nicotinic acetylcholine receptors
Journal
International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
Titre abrégé: Int J Parasitol Drugs Drug Resist
Pays: Netherlands
ID NLM: 101576715
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
21
12
2019
revised:
13
04
2020
accepted:
14
04
2020
pubmed:
30
5
2020
medline:
17
3
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
Cholinergic agonists, like levamisole, are a major class of anthelmintic drugs 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).
Identifiants
pubmed: 32470835
pii: S2211-3207(20)30007-5
doi: 10.1016/j.ijpddr.2020.04.002
pmc: PMC7256660
pii:
doi:
Substances chimiques
Nicotinic Antagonists
0
RNA, Messenger
0
Receptors, Nicotinic
0
Levamisole
2880D3468G
Acetylcholine
N9YNS0M02X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
38-50Subventions
Organisme : NIAID NIH HHS
ID : R01 AI047194
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI092185
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests.
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