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- Title
Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase.
- Authors
Jae Woong Lee; Jung Ho Park; Park, Dong I. L.; Jung-Hwan Park; Hong Joo Kim; Yong Kyun Cho; Sohn, Chong I. L.; Woo Kyu Jeon; Byung Ik Kim; Lee, Jae Woong; Park, Jung Ho; Park, Jung-Hwan; Kim, Hong Joo; Cho, Yong Kyun; Jeon, Woo Kyu; Kim, Byung Ik
- Abstract
<bold>Background and Aims: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
IRRITABLE colon; DIARRHEA; INTESTINAL diseases; PEROXIDASE; POLYMERASE chain reaction; SERINE proteinases; BIOPSY; MUCOUS membranes; PATIENTS; CELL culture; CELL physiology; CELL receptors; COLON (Anatomy); DOSE-effect relationship in pharmacology; HYDROLASES; INTESTINAL mucosa; OXIDOREDUCTASES; RECTUM; REVERSE transcriptase polymerase chain reaction; IN vitro studies
- Publication
Digestive Diseases & Sciences, 2010, Vol 55, Issue 10, p2922
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-009-1094-8