title: Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase.
abstract: OBJECTIVE
  Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability.
  
  
  METHODS
  Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects.
  
  
  RESULTS
  When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P < 0.05) and was abolished by the addition of tryptase inhibitor (100 μM nafamostat; 1.568 ± 0.874 ng/2 h/mm(2) to 0.766 ± 0.661 ng/2 h/mm(2), n = 14, respectively, P < 0.01). Intestinal permeability in patients with IBS-D was significantly increased compared with controls (0.848 ± 0.0.600 ng/2 h/mm(2), n = 21, P < 0.01). Nafamostat significantly reduced the enhanced permeability in IBS-D (0.934 ± 0.589 ng/2 h/mm(2) to 0.247 ± 0.263 ng/2 h/mm(2), n = 14, respectively, P < 0.05). Transcription levels of PAR2 measured by RT-PCR did not differ between IBS-D and normal subjects.
  
  
  CONCLUSIONS
  Tryptase seems to play an important role in the control of human colonic mucosal permeability, and enhanced tryptase activity was responsible for the increased permeability of rectal mucosa in IBS patients.
authors.affiliation: Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Dong I L
authors.initials: DI
authors.lastname: Park
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
authors.forename: Chong I L
authors.initials: CI
authors.lastname: Sohn
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Jeon
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Kim
mesh_terms: D001706:Biopsy; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003967:Diarrhea / Q000378:metabolism* / Q000473:pathology; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D006735:Horseradish Peroxidase; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000473:pathology; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053802:Tryptases / Q000494:pharmacology / Q000502:physiology*
chemical_list: D044464:Receptor, PAR-2; D006735:Horseradish Peroxidase; D053802:Tryptases