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Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.
- Source :
-
Neurogastroenterology and motility [Neurogastroenterol Motil] 2012 Dec; Vol. 24 (12), pp. 1118-e570. Date of Electronic Publication: 2012 Sep 02. - Publication Year :
- 2012
-
Abstract
- Background: Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled.<br />Methods: Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors.<br />Key Results: Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect.<br />Conclusions & Inferences: Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.<br /> (© 2012 Blackwell Publishing Ltd.)
- Subjects :
- Adult
Animals
Colon immunology
Colon metabolism
Colon pathology
Female
Guinea Pigs
Humans
Intestinal Mucosa immunology
Intestinal Mucosa pathology
Irritable Bowel Syndrome immunology
Irritable Bowel Syndrome pathology
Male
Mast Cells immunology
Mast Cells pathology
Motor Neurons metabolism
Myenteric Plexus metabolism
Cholinergic Neurons metabolism
Culture Media, Conditioned pharmacology
Intestinal Mucosa metabolism
Irritable Bowel Syndrome metabolism
Mast Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2982
- Volume :
- 24
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Neurogastroenterology and motility
- Publication Type :
- Academic Journal
- Accession number :
- 22937879
- Full Text :
- https://doi.org/10.1111/nmo.12000