Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting

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dc.contributor.author Hagbom, M en
dc.contributor.author Istrate, C en
dc.contributor.author Engblom, D en
dc.contributor.author Karlsson, T en
dc.contributor.author Rodriguez-Diaz, J en
dc.contributor.author Buesa, J en
dc.contributor.author Taylor, John en
dc.contributor.author Loitto, VM en
dc.contributor.author Magnusson, KE en
dc.contributor.author Ahlman, H en
dc.contributor.author Lundgren, O en
dc.contributor.author Svensson, L en
dc.date.accessioned 2012-03-08T02:12:13Z en
dc.date.issued 2011 en
dc.identifier.citation PLoS Pathogens 7(7):10 pages Article number e1002115 2011 en
dc.identifier.issn 1553-7366 en
dc.identifier.uri http://hdl.handle.net/2292/13422 en
dc.description.abstract Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca2+ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP3), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT3 receptor antagonists. en
dc.language EN en
dc.publisher Public Library of Science en
dc.relation.ispartofseries PLOS Pathogens en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: http://www.sherpa.ac.uk/romeo/issn/1553-7366/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ en
dc.subject IRRITABLE-BOWEL-SYNDROME en
dc.subject ENTERIC NERVOUS-SYSTEM en
dc.subject NONSTRUCTURAL GLYCOPROTEIN NSP4 en
dc.subject CHEMOTHERAPY-INDUCED NAUSEA en
dc.subject INTESTINAL FLUID SECRETION en
dc.subject INTRACELLULAR CALCIUM en
dc.subject ACUTE GASTROENTERITIS en
dc.subject ORAL ONDANSETRON en
dc.subject EPITHELIAL-CELLS en
dc.subject CHOLERA-TOXIN en
dc.title Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting en
dc.type Journal Article en
dc.identifier.doi 10.1371/journal.ppat.1002115 en
pubs.issue 7 en
pubs.volume 7 en
dc.rights.holder Copyright: Public Library of Science en
dc.identifier.pmid 21779163 en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Article en
pubs.elements-id 219493 en
pubs.org-id Science en
pubs.org-id Biological Sciences en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
pubs.number e1002115 en
pubs.record-created-at-source-date 2012-02-27 en
pubs.dimensions-id 21779163 en


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