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dc.contributor.authorYu, Yang
dc.contributor.authorVillalobos- Hernandez, Egina
dc.contributor.authorPradhananga, Sabindra
dc.contributor.authorBaker, Corey
dc.contributor.authorKeating, Christopher
dc.contributor.authorGrundy, David
dc.contributor.authorLomax, Allan
dc.contributor.authorReed, David
dc.date.accessioned2019-09-10T15:31:28Z
dc.date.available2019-09-10T15:31:28Z
dc.date.issued2019-09-01
dc.identifier.citationYu , Y , Villalobos- Hernandez , E , Pradhananga , S , Baker , C , Keating , C , Grundy , D , Lomax , A & Reed , D 2019 , ' Deoxycholic acid activates colonic afferent nerves via 5-HT3 receptor dependent and independent mechanisms ' , American Journal of Physiology - Gastrointestinal and Liver Physiology , vol. 317 , no. 3 , pp. G275-G284 . https://doi.org/10.1152/ajpgi.00016.2019
dc.identifier.issn0193-1857
dc.identifier.otherPURE: 17058712
dc.identifier.otherPURE UUID: a0897e7e-6f59-48ba-a631-35472764c868
dc.identifier.otherScopus: 85071714636
dc.identifier.urihttp://hdl.handle.net/2299/21667
dc.description.abstractIncreased bile acids in the colon can evoke increased epithelial secretion resulting in diarrhea, but little is known about whether colonic bile acids contribute to abdominal pain. This study aimed to investigate the mechanisms underlying activation of colonic extrinsic afferent nerves and their neuronal cell bodies by a major secondary bile acid, deoxycholic acid (DCA). All experiments were performed on male C57BL/6 mice. Afferent sensitivity was evaluated using in vitro extracellular recordings from mesenteric nerves in the proximal colon (innervated by vagal and spinal afferents) and distal colon (spinal afferents only). Neuronal excitability of cultured dorsal root ganglion (DRG) and nodose ganglion (NG) neurons was examined with perforated patch clamp. Colonic 5-HT release was assessed using ELISA, and 5-HT immunoreactive enterochromaffin (EC) cells were quantified. Intraluminal DCA increased afferent nerve firing rate concentration dependently in both proximal and distal colon. This DCA-elicited increase was significantly inhibited by a 5-HT3 antagonist in the proximal colon but not in the distal colon, which may be in part due to lower 5-HT immunoreactive EC cell density and lower 5-HT levels in the distal colon following DCA stimulation. DCA increased the excitability of DRG neurons, whereas it decreased the excitability of NG neurons. DCA potentiated mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. Together, this study suggests that DCA can excite colonic afferents via direct and indirect mechanisms but the predominant mechanism may differ between vagal and spinal afferents. Furthermore, DCA increased mechanosensitivity of high-threshold spinal afferents and may be a mechanism of visceral hypersensitivity.NEW & NOTEWORTHY Deoxycholic acid (DCA) directly excites spinal afferents and, to a lesser extent, indirectly via mucosal 5-HT release. DCA potentiates mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. DCA increases vagal afferent firing in proximal colon via 5-HT release but directly inhibits the excitability of their cell bodies.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
dc.rightsEmbargoed
dc.subject5-HT
dc.subjectbile acid
dc.subjecthypersensitivity
dc.subjectspinal afferent
dc.subjectvagal afferent
dc.subjectPhysiology
dc.subjectHepatology
dc.subjectGastroenterology
dc.subjectPhysiology (medical)
dc.titleDeoxycholic acid activates colonic afferent nerves via 5-HT3 receptor dependent and independent mechanismsen
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionBasic and Clinical Science Unit
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.date.embargoedUntil2020-08-28
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85071714636&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Accepted Version
dcterms.dateAccepted2019-09-01
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1152/ajpgi.00016.2019
rioxxterms.licenseref.uriOther
rioxxterms.licenseref.startdate2020-08-28
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.date.embargo2020-08-28
herts.rights.accesstypeEmbargoed


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