Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients
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.
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.
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.
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.
KeywordsIrritable bowel syndrome (IBS) Protease-activated receptors (PARs) Serotonin (5-HT)
- 2.Foxx-Orenstein A. IBS—review and what’s new. Med Gen Med. 2006;8:20.Google Scholar
- 11.Coelho A, Bunnett NW. Intestinal activation of proteinase-activated receptor-1 (PAR1) reduces visceral nociception associated to rectal distension (RD) in rats. Gastroenterology 2003;124:A-1.Google Scholar
- 13.Vergnolle N, Cellars L, Chapman K. Proteinase-activated receptor-1 agonists attenuate visceral pain. Gastroenterology 2003;124:A-252.Google Scholar
- 22.Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47:804–11.PubMedCrossRefGoogle Scholar
- 25.Miwa J, Echizen H, Matsueda K, Umeda N. Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits. Digestion. 2001;63:188–94.PubMedCrossRefGoogle Scholar
- 26.Drossman DA, Corrazziari E, Delvaux M, Spiller RC, Talley NJ, Thompson WG, et al. Rome III: the functional gastrointestinal disorders diagnosis, pathophysiology, and treatment: a multinational consensus. Mclean, VA: Degnon Association; 2006.Google Scholar