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Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production

Human clonorchiasis, caused by Clonorchis sinensis, is endemic in East Asian countries. C. sinensis metacercariae excyst in the duodenum of mammalian hosts, migrate to the intrahepatic bile duct, and mature into adults in the milieu of bile. We have previously shown that newly excysted juvenile C. s...

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Autores principales: Dai, Fuhong, Song, Jin-Ho, Hong, Yeon Pyo, Bai, Xuelian, Sohn, Woon-Mok, Hong, Sung-Jong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145267/
https://www.ncbi.nlm.nih.gov/pubmed/32226018
http://dx.doi.org/10.1371/journal.pntd.0008220
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author Dai, Fuhong
Song, Jin-Ho
Hong, Yeon Pyo
Bai, Xuelian
Sohn, Woon-Mok
Hong, Sung-Jong
author_facet Dai, Fuhong
Song, Jin-Ho
Hong, Yeon Pyo
Bai, Xuelian
Sohn, Woon-Mok
Hong, Sung-Jong
author_sort Dai, Fuhong
collection PubMed
description Human clonorchiasis, caused by Clonorchis sinensis, is endemic in East Asian countries. C. sinensis metacercariae excyst in the duodenum of mammalian hosts, migrate to the intrahepatic bile duct, and mature into adults in the milieu of bile. We have previously shown that newly excysted juvenile C. sinensis move chemotactically toward bile and bile acids. Here, the chemotactic behavior of adult C. sinensis (CsAd) toward bile and bile acids was investigated. CsAds moved toward 0.05–5% bile and were most attracted to 0.5% bile but moved away from 10% bile. Upon exposure to 1–10% bile, CsAds eventually stopped moving and then died quickly. Among bile acids, CsAds showed strong chemotaxis toward cholic acid (CA) and deoxycholic acid. On the contrary, CsAds repelled from lithocholic acid (LCA). Moreover, at higher than 10 mM LCA, CsAds became sluggish and eventually died. Dopamine D(1) receptor antagonists (LE-300 and SKF-83566), D(2/3) receptor antagonists (raclopride and its derivative CS-49612), and a dopamine re-uptake inhibitor inhibited CA-induced chemotaxis of CsAds almost completely. Clinically used antipsychotic drugs, namely chlorpromazine, haloperidol, and clozapine, are dopaminergic antagonists and are secreted into bile. They completely inhibited chemotaxis of CsAds toward CA. At the maximum doses used to treat patients, the three tested medicines only expelled 2–12% of CsAds from the experimentally infected rabbits, but reduced egg production by 64–79%. Thus, antipsychotic medicines with dopaminergic antagonism could be considered as new anthelmintic candidates for human C. sinensis infections.
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spelling pubmed-71452672020-04-21 Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production Dai, Fuhong Song, Jin-Ho Hong, Yeon Pyo Bai, Xuelian Sohn, Woon-Mok Hong, Sung-Jong PLoS Negl Trop Dis Research Article Human clonorchiasis, caused by Clonorchis sinensis, is endemic in East Asian countries. C. sinensis metacercariae excyst in the duodenum of mammalian hosts, migrate to the intrahepatic bile duct, and mature into adults in the milieu of bile. We have previously shown that newly excysted juvenile C. sinensis move chemotactically toward bile and bile acids. Here, the chemotactic behavior of adult C. sinensis (CsAd) toward bile and bile acids was investigated. CsAds moved toward 0.05–5% bile and were most attracted to 0.5% bile but moved away from 10% bile. Upon exposure to 1–10% bile, CsAds eventually stopped moving and then died quickly. Among bile acids, CsAds showed strong chemotaxis toward cholic acid (CA) and deoxycholic acid. On the contrary, CsAds repelled from lithocholic acid (LCA). Moreover, at higher than 10 mM LCA, CsAds became sluggish and eventually died. Dopamine D(1) receptor antagonists (LE-300 and SKF-83566), D(2/3) receptor antagonists (raclopride and its derivative CS-49612), and a dopamine re-uptake inhibitor inhibited CA-induced chemotaxis of CsAds almost completely. Clinically used antipsychotic drugs, namely chlorpromazine, haloperidol, and clozapine, are dopaminergic antagonists and are secreted into bile. They completely inhibited chemotaxis of CsAds toward CA. At the maximum doses used to treat patients, the three tested medicines only expelled 2–12% of CsAds from the experimentally infected rabbits, but reduced egg production by 64–79%. Thus, antipsychotic medicines with dopaminergic antagonism could be considered as new anthelmintic candidates for human C. sinensis infections. Public Library of Science 2020-03-30 /pmc/articles/PMC7145267/ /pubmed/32226018 http://dx.doi.org/10.1371/journal.pntd.0008220 Text en © 2020 Dai et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dai, Fuhong
Song, Jin-Ho
Hong, Yeon Pyo
Bai, Xuelian
Sohn, Woon-Mok
Hong, Sung-Jong
Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title_full Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title_fullStr Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title_full_unstemmed Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title_short Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production
title_sort dopaminergic antagonists inhibit bile chemotaxis of adult clonorchis sinensis and its egg production
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145267/
https://www.ncbi.nlm.nih.gov/pubmed/32226018
http://dx.doi.org/10.1371/journal.pntd.0008220
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