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Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.
PLoS One 2013; 8(12):e84718Plos

Abstract

The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.

Authors+Show Affiliations

Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24367692

Citation

Carroll, Siobhan Yvonne, et al. "Disodium Cromoglycate Reverses Colonic Visceral Hypersensitivity and Influences Colonic Ion Transport in a Stress-sensitive Rat Strain." PloS One, vol. 8, no. 12, 2013, pp. e84718.
Carroll SY, O'Mahony SM, Grenham S, et al. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain. PLoS ONE. 2013;8(12):e84718.
Carroll, S. Y., O'Mahony, S. M., Grenham, S., Cryan, J. F., & Hyland, N. P. (2013). Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain. PloS One, 8(12), pp. e84718. doi:10.1371/journal.pone.0084718.
Carroll SY, et al. Disodium Cromoglycate Reverses Colonic Visceral Hypersensitivity and Influences Colonic Ion Transport in a Stress-sensitive Rat Strain. PLoS ONE. 2013;8(12):e84718. PubMed PMID: 24367692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain. AU - Carroll,Siobhan Yvonne, AU - O'Mahony,Siobhain Mary, AU - Grenham,Susan, AU - Cryan,John Francis, AU - Hyland,Niall Patrick, Y1 - 2013/12/18/ PY - 2013/08/02/received PY - 2013/11/18/accepted PY - 2013/12/25/entrez PY - 2013/12/25/pubmed PY - 2014/7/30/medline SP - e84718 EP - e84718 JF - PloS one JO - PLoS ONE VL - 8 IS - 12 N2 - The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24367692/Disodium_cromoglycate_reverses_colonic_visceral_hypersensitivity_and_influences_colonic_ion_transport_in_a_stress_sensitive_rat_strain_ L2 - http://dx.plos.org/10.1371/journal.pone.0084718 DB - PRIME DP - Unbound Medicine ER -