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dc.contributor.authorBautzova, Terezaen
dc.contributor.authorHockley, Jamesen
dc.contributor.authorPerez-Berezo, Teresaen
dc.contributor.authorPujo, Julienen
dc.contributor.authorTranter, Michael Men
dc.contributor.authorDesormeaux, Cleoen
dc.contributor.authorBarbaro, Maria Raffaellaen
dc.contributor.authorBasso, Lilianen
dc.contributor.authorLe Faouder, Paulineen
dc.contributor.authorRolland, Corinneen
dc.contributor.authorMalapert, Pascaleen
dc.contributor.authorMoqrich, Azizen
dc.contributor.authorEutamene, Heleneen
dc.contributor.authorDenadai-Souza, Alexandreen
dc.contributor.authorVergnolle, Nathalieen
dc.contributor.authorSmith, Ewan St Johnen
dc.contributor.authorHughes, David Ien
dc.contributor.authorBarbara, Giovannien
dc.contributor.authorDietrich, Gillesen
dc.contributor.authorBulmer, Daviden
dc.contributor.authorCenac, Nicolasen
dc.date.accessioned2019-01-05T00:30:18Z
dc.date.available2019-01-05T00:30:18Z
dc.date.issued2018-12-18en
dc.identifier.issn1945-0877
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287543
dc.description.abstractIrritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites such as prostaglandin E2 (PGE2) are elevated in IBS and implicated in visceral hypersensitivity. The aim of this study was to quantify PUFA metabolites in IBS patients and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increase in 5-oxo-eicosatetraenoic acid (5-oxoETE) only in biopsies taken from IBS with predominant constipation (IBS-C) patients. Local 5-oxoETE administration induced somatic and visceral hypersensitivity with no tissue inflammation. 5-oxoETE directly acts on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+-imaging of dorsal root ganglia (DRG) neurons. 5-oxoETE selectively stimulated isolectin B4 (IB4)-positive DRG neurons through a PLC and pertussis toxin-dependent mechanism, suggesting a G-protein coupled receptor-mediated effect. The MAS-related G protein coupled receptor D (Mrgprd) was found in mouse colonic DRG afferents and was identified as the target receptor for 5-oxoETE. In conclusion, 5-oxoETE, a potential biomarker of IBS-C, activates Mrgprd in nociceptors and induces somatic and visceral hyperalgesia without inflammation. Thus, 5-oxoETE may play a pivotal role in abdominal pain associated with IBS-C.
dc.description.sponsorshipBBSRC BB/R006210/1 to James R F Hockley and Ewan St John Smith Rosetrees 834 Postdoctoral Grant (A1296) awarded to James R F Hockley and Ewan St John Smith
dc.format.mediumElectronicen
dc.languageengen
dc.publisherAmerican Association for the Advancement of Science
dc.subjectColonen
dc.subjectGanglia, Spinalen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectIrritable Bowel Syndromeen
dc.subjectConstipationen
dc.subjectCalciumen
dc.subjectArachidonic Acidsen
dc.subjectReceptors, G-Protein-Coupleden
dc.subjectCase-Control Studiesen
dc.subjectSignal Transductionen
dc.subjectMaleen
dc.subjectSensory Receptor Cellsen
dc.subjectNociceptionen
dc.title5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.en
dc.typeArticle
prism.issueIdentifier561en
prism.publicationDate2018en
prism.publicationNameScience signalingen
prism.volume11en
dc.identifier.doi10.17863/CAM.34853
dcterms.dateAccepted2018-08-10en
rioxxterms.versionofrecord10.1126/scisignal.aal2171en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12-18en
dc.contributor.orcidHockley, James [0000-0002-9578-6071]
dc.contributor.orcidPujo, Julien [0000-0002-1464-8380]
dc.contributor.orcidTranter, Michael M [0000-0001-9130-1033]
dc.contributor.orcidBarbaro, Maria Raffaella [0000-0003-4438-554X]
dc.contributor.orcidDenadai-Souza, Alexandre [0000-0003-0385-1321]
dc.contributor.orcidVergnolle, Nathalie [0000-0003-1825-6015]
dc.contributor.orcidSmith, Ewan [0000-0002-2699-1979]
dc.contributor.orcidHughes, David I [0000-0003-1260-3362]
dc.contributor.orcidDietrich, Gilles [0000-0002-2232-1716]
dc.contributor.orcidBulmer, David [0000-0002-4703-7877]
dc.contributor.orcidCenac, Nicolas [0000-0002-1552-7812]
dc.identifier.eissn1937-9145
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idRosetrees Trust (A1296)
pubs.funder-project-idBBSRC (BB/R006210/1)


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