Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase.
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.
Lee
Jae Woong
JW
Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Park
Jung Ho
JH
Park
Dong I L
DI
Park
Jung-Hwan
JH
Kim
Hong Joo
HJ
Cho
Yong Kyun
YK
Sohn
Chong I L
CI
Jeon
Woo Kyu
WK
Kim
Byung Ik
BI
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*
D044464:Receptor, PAR-2; D006735:Horseradish Peroxidase; D053802:Tryptases