title: Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.
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.
  
  
  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.
  
  
  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
  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.
authors.affiliation: Department of Forensic Medicine, Pharmacology and Toxicology, University of Pavia, Pavia, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Balestra
authors.forename: R
authors.initials: R
authors.lastname: Vicini
authors.forename: C
authors.initials: C
authors.lastname: Cremon
authors.forename: L
authors.initials: L
authors.lastname: Zecchi
authors.forename: G
authors.initials: G
authors.lastname: Dothel
authors.forename: V
authors.initials: V
authors.lastname: Vasina
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
authors.forename: A
authors.initials: A
authors.lastname: Paccapelo
authors.forename: O
authors.initials: O
authors.lastname: Pastoris
authors.forename: V
authors.initials: V
authors.lastname: Stanghellini
authors.forename: R
authors.initials: R
authors.lastname: Corinaldesi
authors.forename: F
authors.initials: F
authors.lastname: De Ponti
authors.forename: M
authors.initials: M
authors.lastname: Tonini
authors.forename: G
authors.initials: G
authors.lastname: Barbara
mesh_terms: D000328:Adult; D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism; D009197:Myenteric Plexus / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned