Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients.
OBJECTIVE
The aim of this study is to determine whether a changed expression ratio of PAR-1 and PAR-2 in the colon is associated with diarrhea-predominant IBS patients.


METHODS
PAR-1, -2, thrombin, mast cell tryptase, tryptophan hydroxylase (TPH), and chromgranin A (ChrA) in colonic biopsy samples from 10 diarrhea-predominant IBS patients and 13 healthy control subjects were semiquantified with immunofluorescence and image analysis. Serotonin concentrations in biopsy samples were evaluated by capillary electrophoresis.


RESULTS
Significantly lower expression of PAR-1 and higher expression of mast cell tryptase was detected in the colons of patients, with statistically unchanged expression of PAR-2. Thrombin-, TPH-, and ChrA-positive cells were markedly increased in IBS patients, but no significant difference in serotonin concentration existed in the colons between two groups. The ratio of PAR-1/PAR-2 expression was significantly decreased in patients (0.33+/-0.19 versus 0.66+/-0.22, P=0.001) and negatively correlated to ChrA-positive cells.


CONCLUSIONS
Changed expression ratio of PAR-1 to PAR-2 in the colon is connected with diarrhea-predominant IBS patients. Methods to restore an appropriate balance of PAR-1 and PAR-2 activation in the colon may offer a promising future therapeutic strategy for IBS patients.
Bian
Zhao Xiang
ZX
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China. bzxiang@hkbu.edu.hk
Li
Zhi
Z
Huang
Zhi Xin
ZX
Zhang
Man
M
Chen
Hong Li
HL
Xu
Hong Xi
HX
Sung
Joseph J Y
JJ
D000328:Adult; D000368:Aged; D001706:Biopsy; D002452:Cell Count; D003106:Colon / Q000378:metabolism; D003967:Diarrhea / Q000378:metabolism*; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D044463:Receptor, PAR-1 / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D013917:Thrombin; D053802:Tryptases