These authors equally contributed to the manuscript.
Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons
Article first published online: 2 SEP 2012
© 2012 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 12, pages 1118–e570, December 2012
How to Cite
Balestra, B., Vicini, R., Cremon, C., Zecchi, L., Dothel, G., Vasina, V., De Giorgio, R., Paccapelo, A., Pastoris, O., Stanghellini, V., Corinaldesi, R., De Ponti, F., Tonini, M. and Barbara, G. (2012), Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons. Neurogastroenterology & Motility, 24: 1118–e570. doi: 10.1111/nmo.12000
- Issue published online: 26 NOV 2012
- Article first published online: 2 SEP 2012
- Received: 22 June 2012 Accepted for publication: 10 July 2012
- enteric nervous system;
- inflammatory mucosal mediators;
- irritable bowel syndrome;
- mast cells;
- twitch contractions
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.
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.
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.
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.