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.author Buckley, Maria M.
dc.contributor.author O'Brien, Rebecca
dc.contributor.author Buckley, Julliette M.
dc.contributor.author O'Malley, Dervla
dc.date.accessioned 2019-08-14T10:37:13Z
dc.date.available 2019-08-14T10:37:13Z
dc.date.issued 2019-07-16
dc.identifier.citation 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 en
dc.identifier.startpage 1 en
dc.identifier.endpage 13 en
dc.identifier.issn 1350-1925
dc.identifier.uri http://hdl.handle.net/10468/8316
dc.identifier.doi 10.1111/nmo.13684 en
dc.description.abstract Background: 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.sponsorship University College Cork (Translational Research Access Programme (TRAP) funding, School of Medicine) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher John Wiley & Sons, Inc. en
dc.relation.uri https://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.subject Colonic contractility en
dc.subject Ghrelin en
dc.subject Glucagon-like peptide 1 en
dc.subject Myenteric en
dc.subject Vagal en
dc.title 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? en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Dervla O'Malley, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: d.omalley@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2020-07-16
dc.date.updated 2019-08-14T10:26:34Z
dc.description.version Accepted Version en
dc.internal.rssid 495368170
dc.contributor.funder University College Cork en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neurogastroenterology and Motility en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress d.omalley@ucc.ie en
dc.identifier.articleid e13684 en
dc.internal.bibliocheck Early View - Online Version of Record before inclusion in an issue. Check vol / issue / page range. Amend citation as necessary. en
dc.identifier.eissn 1365-2982


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