GHSR-1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin-4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?

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dc.contributor.authorBuckley, Maria M.
dc.contributor.authorO'Brien, Rebecca
dc.contributor.authorBuckley, Julliette M.
dc.contributor.authorO'Malley, Dervla
dc.contributor.funderUniversity College Corken
dc.date.accessioned2019-08-14T10:37:13Z
dc.date.available2019-08-14T10:37:13Z
dc.date.issued2019-07-16
dc.date.updated2019-08-14T10:26:34Z
dc.description.abstractBackground: Patients with irritable bowel syndrome (IBS) may experience postprandial symptom exacerbation. Nutrients stimulate intestinal release of glucagon‐like peptide 1 (GLP‐1), an incretin hormone with known gastrointestinal effects. However, prior to the postprandial rise in GLP‐1, levels of the hunger hormone, ghrelin, peak. The aims of this study were to determine if ghrelin sensitizes colonic intrinsic and extrinsic neurons to the stimulatory actions of a GLP‐1 receptor agonist, and if this differs in a rat model of IBS. Methods: Calcium imaging of enteric neurons was compared between Sprague Dawley and Wistar Kyoto rats. Colonic contractile activity and vagal nerve recordings were also compared between strains. Key Results: Circulating GLP‐1 concentrations differ between IBS subtypes. Mechanistically, we have provided evidence that calcium responses evoked by exendin‐4, a GLP‐1 receptor agonist, are potentiated by a ghrelin receptor (GHSR‐1) agonist, in both submucosal and myenteric neurons. Although basal patterns of colonic contractility varied between Sprague Dawley and Wister Kyoto rats, the capacity of exendin‐4 to alter smooth muscle function was modified by a GHSR‐1 agonist in both strains. Gut‐brain signaling via GLP‐1–mediated activation of vagal afferents was also potentiated by the GHSR‐1 agonist. Conclusions & Inferences: These findings support a temporal interaction between ghrelin and GLP‐1, where the preprandial peak in ghrelin may temporarily sensitize colonic intrinsic and extrinsic neurons to the neurostimulatory actions of GLP‐1. While the sensitizing effects of the GHSR‐1 agonist were identified in both rat strains, in the rat model of IBS, underlying contractile activity was aberrant.en
dc.description.sponsorshipUniversity College Cork (Translational Research Access Programme (TRAP) funding, School of Medicine)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide13684en
dc.identifier.citationBuckley, M. M., O'Brien, R., Buckley, J. M. and O'Malley, D. (2019) 'GHSR-1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin-4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?', Neurogastroenterology and Motility, e13684 (13pp). doi: 10.1111/nmo.13684en
dc.identifier.doi10.1111/nmo.13684en
dc.identifier.eissn1365-2982
dc.identifier.endpage13en
dc.identifier.issn1350-1925
dc.identifier.journaltitleNeurogastroenterology and Motilityen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8316
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.relation.urihttps://onlinelibrary.wiley.com/doi/epdf/10.1111/nmo.13684
dc.rights© 2019, John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Buckley, M. M., O'Brien, R., Buckley, J. M. and O'Malley, D. (2019) 'GHSR-1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin-4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?', Neurogastroenterology and Motility, e13684 (13pp). doi: 10.1111/nmo.13684, which has been published in final form at https://doi.org/10.1111/nmo.13684. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.subjectColonic contractilityen
dc.subjectGhrelinen
dc.subjectGlucagon-like peptide 1en
dc.subjectMyentericen
dc.subjectVagalen
dc.titleGHSR-1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin-4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?en
dc.typeArticle (peer-reviewed)en
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