Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro-antagonists

The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts, and the newly excysted juveniles (CsNEJs) migrate along the bile duct via bile chemotaxis. Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of...

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Veröffentlicht in:PLoS neglected tropical diseases 2019-08, Vol.13 (8), p.e0007573-e0007573
Hauptverfasser: Li, Shunyu, Song, Jin-Ho, Kim, Tae Im, Yoo, Won Gi, Won, Moo-Ho, Dai, Fuhong, Hong, Sung-Jong
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container_title PLoS neglected tropical diseases
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creator Li, Shunyu
Song, Jin-Ho
Kim, Tae Im
Yoo, Won Gi
Won, Moo-Ho
Dai, Fuhong
Hong, Sung-Jong
description The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts, and the newly excysted juveniles (CsNEJs) migrate along the bile duct via bile chemotaxis. Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of chemotactic behavior of CsNEJs toward cholic acid. The migration of CsNEJs was strongly inhibited at sub-micromolar concentration by dopamine D1 (LE-300 and SKF-83566), D2 (spiramide, nemonapride, and sulpiride), and D3 (GR-103691 and NGB-2904) receptor antagonists, as well as a dopamine reuptake inhibitor (BTCP). Neuropeptides, FMRFamide, peptide YY, and neuropeptide Y were also potent inhibitors of chemotaxis. Meanwhile, serotonergic, glutamatergic, and cholinergic inhibitors did not affect chemotaxis, with the exception of fluoxetine and CNQX. Confocal immunofluorescence analysis indicated that dopaminergic and cholinergic neurons were colocalized in the somatic muscle tissues of adult C. sinensis. Our findings suggest that dopaminergic neurons and neuropeptides play a major role in the chemotactic migration of CsNEJs to bile, and their inhibitors or modulators could be utilized to prevent their migration from the bile duct.
doi_str_mv 10.1371/journal.pntd.0007573
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Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of chemotactic behavior of CsNEJs toward cholic acid. The migration of CsNEJs was strongly inhibited at sub-micromolar concentration by dopamine D1 (LE-300 and SKF-83566), D2 (spiramide, nemonapride, and sulpiride), and D3 (GR-103691 and NGB-2904) receptor antagonists, as well as a dopamine reuptake inhibitor (BTCP). Neuropeptides, FMRFamide, peptide YY, and neuropeptide Y were also potent inhibitors of chemotaxis. Meanwhile, serotonergic, glutamatergic, and cholinergic inhibitors did not affect chemotaxis, with the exception of fluoxetine and CNQX. Confocal immunofluorescence analysis indicated that dopaminergic and cholinergic neurons were colocalized in the somatic muscle tissues of adult C. sinensis. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of chemotactic behavior of CsNEJs toward cholic acid. The migration of CsNEJs was strongly inhibited at sub-micromolar concentration by dopamine D1 (LE-300 and SKF-83566), D2 (spiramide, nemonapride, and sulpiride), and D3 (GR-103691 and NGB-2904) receptor antagonists, as well as a dopamine reuptake inhibitor (BTCP). Neuropeptides, FMRFamide, peptide YY, and neuropeptide Y were also potent inhibitors of chemotaxis. Meanwhile, serotonergic, glutamatergic, and cholinergic inhibitors did not affect chemotaxis, with the exception of fluoxetine and CNQX. Confocal immunofluorescence analysis indicated that dopaminergic and cholinergic neurons were colocalized in the somatic muscle tissues of adult C. sinensis. 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pharmacology</topic><topic>Bile</topic><topic>Bile ducts</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Biphenyl Compounds - pharmacology</topic><topic>Care and treatment</topic><topic>Cell migration</topic><topic>Chemotaxis</topic><topic>Chemotaxis - drug effects</topic><topic>Chemotaxis - physiology</topic><topic>Cholic Acid</topic><topic>Cholinergics</topic><topic>Cloning</topic><topic>Clonorchis sinensis</topic><topic>Clonorchis sinensis - drug effects</topic><topic>Clonorchis sinensis - physiology</topic><topic>Dopamine</topic><topic>Dopamine - pharmacology</topic><topic>Dopamine D1 receptors</topic><topic>Dopamine D2 receptors</topic><topic>Dopamine D3 receptors</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Duodenum</topic><topic>Excitatory Amino Acid Agents - pharmacology</topic><topic>Fasciola hepatica - drug effects</topic><topic>Fluke infections</topic><topic>Fluorenes - pharmacology</topic><topic>Fluorescent antibody technique</topic><topic>Fluoxetine</topic><topic>FMRFamide</topic><topic>FMRFamide - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Shunyu</au><au>Song, Jin-Ho</au><au>Kim, Tae Im</au><au>Yoo, Won Gi</au><au>Won, Moo-Ho</au><au>Dai, Fuhong</au><au>Hong, Sung-Jong</au><au>Chai, Jong-Yil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro-antagonists</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2019-08-13</date><risdate>2019</risdate><volume>13</volume><issue>8</issue><spage>e0007573</spage><epage>e0007573</epage><pages>e0007573-e0007573</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts, and the newly excysted juveniles (CsNEJs) migrate along the bile duct via bile chemotaxis. Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of chemotactic behavior of CsNEJs toward cholic acid. The migration of CsNEJs was strongly inhibited at sub-micromolar concentration by dopamine D1 (LE-300 and SKF-83566), D2 (spiramide, nemonapride, and sulpiride), and D3 (GR-103691 and NGB-2904) receptor antagonists, as well as a dopamine reuptake inhibitor (BTCP). Neuropeptides, FMRFamide, peptide YY, and neuropeptide Y were also potent inhibitors of chemotaxis. Meanwhile, serotonergic, glutamatergic, and cholinergic inhibitors did not affect chemotaxis, with the exception of fluoxetine and CNQX. Confocal immunofluorescence analysis indicated that dopaminergic and cholinergic neurons were colocalized in the somatic muscle tissues of adult C. sinensis. Our findings suggest that dopaminergic neurons and neuropeptides play a major role in the chemotactic migration of CsNEJs to bile, and their inhibitors or modulators could be utilized to prevent their migration from the bile duct.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31408466</pmid><doi>10.1371/journal.pntd.0007573</doi><orcidid>https://orcid.org/0000-0002-8677-4714</orcidid><orcidid>https://orcid.org/0000-0002-3041-5560</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acids
Animals
Antidepressants
Benzamides - pharmacology
Bile
Bile ducts
Biology
Biology and Life Sciences
Biphenyl Compounds - pharmacology
Care and treatment
Cell migration
Chemotaxis
Chemotaxis - drug effects
Chemotaxis - physiology
Cholic Acid
Cholinergics
Cloning
Clonorchis sinensis
Clonorchis sinensis - drug effects
Clonorchis sinensis - physiology
Dopamine
Dopamine - pharmacology
Dopamine D1 receptors
Dopamine D2 receptors
Dopamine D3 receptors
Dopamine Uptake Inhibitors - pharmacology
Duodenum
Excitatory Amino Acid Agents - pharmacology
Fasciola hepatica - drug effects
Fluke infections
Fluorenes - pharmacology
Fluorescent antibody technique
Fluoxetine
FMRFamide
FMRFamide - pharmacology
Glutamatergic transmission
Immunofluorescence
Immunomodulation
Inhibitors
Juveniles
Laboratory animals
Liver
Medicine
Migratory species
Minors
Modulators
Motility
Muscles
Nervous system
Neuromodulation
Neurons
Neuropeptide Y
Neuropeptide Y - pharmacology
Neuropeptides
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Neurotransmitter Agents - pharmacology
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Parasitology
Peptide YY - pharmacology
Peptides
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Physical Sciences
Piperazines - pharmacology
Pirenzepine
Proteins
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Serotonin
Serotonin Agents - pharmacology
Spiro Compounds - pharmacology
Sulpiride
Sulpiride - pharmacology
Tropical diseases
University colleges
title Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro-antagonists
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