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dc.contributor.authorKoo, Ada
dc.contributor.authorPustovit, Ruslan V
dc.contributor.authorWoodward, Orla RM
dc.contributor.authorLewis, Jo E
dc.contributor.authorGribble, Fiona M
dc.contributor.authorHossain, Mohammed Akhter
dc.contributor.authorReimann, Frank
dc.contributor.authorFurness, John B
dc.date.accessioned2022-06-15T15:01:05Z
dc.date.available2022-06-15T15:01:05Z
dc.date.issued2022-07
dc.date.submitted2022-02-06
dc.identifier.issn0302-766X
dc.identifier.others00441-022-03635-8
dc.identifier.other3635
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338120
dc.descriptionFunder: University of Melbourne
dc.description.abstractThe gastrointestinal hormone, insulin-like peptide 5 (INSL5), is found in large intestinal enteroendocrine cells (EEC). One of its functions is to stimulate nerve circuits that increase propulsive activity of the colon through its receptor, the relaxin family peptide 4 receptor (RXFP4). To investigate the mechanisms that link INSL5 to stimulation of propulsion, we have determined the localisation of cells expressing Rxfp4 in the mouse colon, using a reporter mouse to locate cells expressing the gene. The fluorescent signal indicating the location of Rxfp4 expression was in EEC, the greatest overlap of Rxfp4-dependent labelling being with cells containing 5-HT. In fact, > 90% of 5-HT cells were positive for Rxfp4 labelling. A small proportion of cells with Rxfp4-dependent labelling was 5-HT-negative, 11-15% in the distal colon and rectum, and 35% in the proximal colon. Of these, some were identified as L-cells by immunoreactivity for oxyntomodulin. Rxfp4-dependent fluorescence was also found in a sparse population of nerve endings, where it was colocalised with CGRP. We used the RXFP4 agonist, INSL5-A13, to activate the receptor and probe the role of the 5-HT cells in which it is expressed. INSL5-A13 administered by i.p. injection to conscious mice caused an increase in colorectal propulsion that was antagonised by the 5-HT3 receptor blocker, alosetron, also given i.p. We conclude that stimuli that excite INSL5-containing colonic L-cells release INSL5 that, through RXFP4, excites 5-HT release from neighbouring endocrine cells, which in turn acts on 5-HT3 receptors of enteric sensory neurons to elicit propulsive reflexes.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectRegular Article
dc.subjectINSL5
dc.subject5-HT
dc.subjectEnteroendocrine cells
dc.subjectEnteric nervous system
dc.subjectColonic reflexes
dc.titleExpression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine.
dc.typeArticle
dc.date.updated2022-06-15T15:01:04Z
prism.endingPage9
prism.issueIdentifier1
prism.publicationNameCell Tissue Res
prism.startingPage1
prism.volume389
dc.identifier.doi10.17863/CAM.85529
dcterms.dateAccepted2022-05-09
rioxxterms.versionofrecord10.1007/s00441-022-03635-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidKoo, Ada [0000-0003-2414-0852]
dc.contributor.orcidPustovit, Ruslan V [0000-0002-9221-1811]
dc.contributor.orcidFurness, John B [0000-0002-0219-3438]
dc.identifier.eissn1432-0878
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idWellcome Trust (106262/Z/14/Z)
pubs.funder-project-idMRC (MC_UU_00014/3)
pubs.funder-project-idMedical Research Council (MC_UU_12012/3)
cam.issuedOnline2022-05-21


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