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Ghrelin sensitises colonic myenteric neurons to the neurostimulatory effects of glucagonlike peptide‐1 in Sprague Dawley and Wistar Kyoto rats.
Author(s) -
O'Brien Rebecca,
Buckley Maria M.,
O'Malley Dervla
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb363
Subject(s) - ghrelin , medicine , endocrinology , orexigenic , irritable bowel syndrome , enteroendocrine cell , stimulation , receptor , population , hormone , endocrine system , neuropeptide , neuropeptide y receptor , environmental health
Irritable Bowel Syndrome (IBS) is a common functional bowel disorder affecting approximately 10–20% of the population with many experiencing post‐prandial exacerbation of symptoms. Although IBS pathophysiology remains elusive, dysfunctional endocrine signalling has been implicated. Ghrelin is an orexigenic hormone which peaks prior to food ingestion. Glucagon‐like peptide‐1 (GLP‐1) is secreted by L‐cells in the mucosa of the small and large intestine in response to the arrival of nutrients. Previous studies have shown that ghrelin directly primes L‐cells to secrete GLP‐1 and increases GLP‐1 release (Gagnon et al., 2014). The aims of this study were to investigate if ghrelin sensitises colonic enteric neurons for GLP‐1 mediated signalling in two animal models; Sprague Dawley (control) and Wistar Kyoto (stress model of IBS). Immunofluorescence was used to stain for ghrelin and GLP‐1 receptors. Colonic motility was assessed in organ baths, using SD and WKY colonic segments, in response to a GLP‐1 mimetic before and after ghrelin stimulation. Ghrelin and GLP‐1 receptors were expressed in discrete co‐localised clusters in myenteric neurons. GLP‐1 reduced contractile activity in both SD and WKY rat colons. However, this response was potentiated by prior exposure to ghrelin in both circular and longitudinal muscle in Sprague Dawley ((p=0.0116), (p=0.0093), respectively) and Wistar Kyoto ((p= 0.0129), (p=0.0006), respectively) rat colonic segments. Ghrelin sensitises the colon to GLP‐1‐evoked contractile activity. Although similar mechanisms of action were evidence in both species, the baseline contractile activity was aberrant in WKY rats. Support or Funding Information Funded by UCC TRAP funding and the Department of Physiology, University College of Cork This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .