Skip to main content
Top
Published in: Journal of Gastroenterology 7/2009

01-07-2009 | Original Article—Alimentary Tract

Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients

Authors: Zhao Xiang Bian, Zhi Li, Zhi Xin Huang, Man Zhang, Hong Li Chen, Hong Xi Xu, Joseph J. Y. Sung

Published in: Journal of Gastroenterology | Issue 7/2009

Login to get access

Abstract

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.
Literature
1.
go back to reference Thompson WG, Heaton KW, Smyth GT, Smyth C. Irritable bowel syndrome in general practice: prevalence, characteristics, and referral. Gut. 2000;46:78–82.PubMedCrossRef Thompson WG, Heaton KW, Smyth GT, Smyth C. Irritable bowel syndrome in general practice: prevalence, characteristics, and referral. Gut. 2000;46:78–82.PubMedCrossRef
2.
go back to reference Foxx-Orenstein A. IBS—review and what’s new. Med Gen Med. 2006;8:20. Foxx-Orenstein A. IBS—review and what’s new. Med Gen Med. 2006;8:20.
3.
go back to reference Talley NJ, Spiller R. Irritable bowel syndrome: a little understood organic bowel disease? Lancet. 2002;360:555–64.PubMedCrossRef Talley NJ, Spiller R. Irritable bowel syndrome: a little understood organic bowel disease? Lancet. 2002;360:555–64.PubMedCrossRef
4.
go back to reference Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med. 2004;95:419–26.PubMed Schwetz I, Bradesi S, Mayer EA. The pathophysiology of irritable bowel syndrome. Minerva Med. 2004;95:419–26.PubMed
6.
go back to reference Mayer EA, Naliboff BD, Chang L, Coutinho SV. V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2001;280:G519–24.PubMed Mayer EA, Naliboff BD, Chang L, Coutinho SV. V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2001;280:G519–24.PubMed
7.
go back to reference Collins SM, Piche T, Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut. 2001;49:743–5.PubMedCrossRef Collins SM, Piche T, Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut. 2001;49:743–5.PubMedCrossRef
8.
9.
go back to reference Vergnolle N. Modulation of visceral pain and inflammation by protease-activated receptors. Br J Pharmacol. 2004;141:1264–74.PubMedCrossRef Vergnolle N. Modulation of visceral pain and inflammation by protease-activated receptors. Br J Pharmacol. 2004;141:1264–74.PubMedCrossRef
10.
go back to reference Noorbakhsh F, Vergnolle N, Hollenberg MD, Power C. Proteinase-activated receptors in the nervous system. Nat Rev Neurosci. 2003;4:981–90.PubMedCrossRef Noorbakhsh F, Vergnolle N, Hollenberg MD, Power C. Proteinase-activated receptors in the nervous system. Nat Rev Neurosci. 2003;4:981–90.PubMedCrossRef
11.
go back to reference 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. 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.
12.
go back to reference Asfaha S, Brussee V, Chapman K, Zochodne DW, Vergnolle N. Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol. 2002;135:1101–6.PubMedCrossRef Asfaha S, Brussee V, Chapman K, Zochodne DW, Vergnolle N. Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol. 2002;135:1101–6.PubMedCrossRef
13.
go back to reference Vergnolle N, Cellars L, Chapman K. Proteinase-activated receptor-1 agonists attenuate visceral pain. Gastroenterology 2003;124:A-252. Vergnolle N, Cellars L, Chapman K. Proteinase-activated receptor-1 agonists attenuate visceral pain. Gastroenterology 2003;124:A-252.
14.
go back to reference Hollenberg MD, Compton SJ. International Union of Pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol Rev. 2002;54:203–17.PubMedCrossRef Hollenberg MD, Compton SJ. International Union of Pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol Rev. 2002;54:203–17.PubMedCrossRef
15.
go back to reference Vergnolle N, Bunnett NW, Sharkey KA, Brussee V, Compton SJ, Grady EF, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med. 2001;7:821–6.PubMedCrossRef Vergnolle N, Bunnett NW, Sharkey KA, Brussee V, Compton SJ, Grady EF, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med. 2001;7:821–6.PubMedCrossRef
16.
go back to reference Reed DE, Barajas-Lopez C, Cottrell G, Velazquez-Rocha S, Dery O, Grady EF, et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol. 2003;547:531–42.PubMedCrossRef Reed DE, Barajas-Lopez C, Cottrell G, Velazquez-Rocha S, Dery O, Grady EF, et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol. 2003;547:531–42.PubMedCrossRef
17.
go back to reference Cenac N, Andrews CN, Holzhausen M, Chapman K, Cottrell G, Andrade-Gordon P, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest. 2007;117:636–47.PubMedCrossRef Cenac N, Andrews CN, Holzhausen M, Chapman K, Cottrell G, Andrade-Gordon P, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest. 2007;117:636–47.PubMedCrossRef
18.
go back to reference Li Z, Zhang XJ, Xu HX, Sung JJY, Bian ZX. Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats. Eur J Pharmacol. 2009;606(1–3):199–204.PubMedCrossRef Li Z, Zhang XJ, Xu HX, Sung JJY, Bian ZX. Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats. Eur J Pharmacol. 2009;606(1–3):199–204.PubMedCrossRef
19.
go back to reference Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.PubMedCrossRef Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.PubMedCrossRef
20.
go back to reference Grundy D. Serotonin and sensory signalling from the gastrointestinal lumen. J Physiol. 2006;575(Pt 1):1–2.PubMedCrossRef Grundy D. Serotonin and sensory signalling from the gastrointestinal lumen. J Physiol. 2006;575(Pt 1):1–2.PubMedCrossRef
21.
go back to reference Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141:1285–93.PubMedCrossRef Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141:1285–93.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference Crowell MD, Shetzline MA, Moses PL, Mawe GM, Talley NJ. Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function. Curr Opin Investig Drugs. 2004;5:55–60.PubMed Crowell MD, Shetzline MA, Moses PL, Mawe GM, Talley NJ. Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function. Curr Opin Investig Drugs. 2004;5:55–60.PubMed
24.
go back to reference Mawe GM, Coates MD, Moses PL. Review article: intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther. 2006;23:1067–76.PubMedCrossRef Mawe GM, Coates MD, Moses PL. Review article: intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther. 2006;23:1067–76.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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. 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.
27.
go back to reference Sjolund K, Sanden G, Hakanson R, Sundler F. Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology. 1983;85:1120–30.PubMed Sjolund K, Sanden G, Hakanson R, Sundler F. Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology. 1983;85:1120–30.PubMed
28.
go back to reference Du M, Flanigan V, Ma Y. Simultaneous determination of polyamines and catecholamines in PC-12 tumor cell extracts by capillary electrophoresis with laser-induced fluorescence detection. Electrophoresis. 2004;25:1496–502.PubMedCrossRef Du M, Flanigan V, Ma Y. Simultaneous determination of polyamines and catecholamines in PC-12 tumor cell extracts by capillary electrophoresis with laser-induced fluorescence detection. Electrophoresis. 2004;25:1496–502.PubMedCrossRef
29.
go back to reference Kawao N, Ikeda H, Kitano T, Kuroda R, Sekiquchi F, Kataoka K, et al. Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2. J Pharmacol Sci. 2004;94:277–85.PubMedCrossRef Kawao N, Ikeda H, Kitano T, Kuroda R, Sekiquchi F, Kataoka K, et al. Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2. J Pharmacol Sci. 2004;94:277–85.PubMedCrossRef
30.
go back to reference Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology. 2002;122:1035–47.PubMedCrossRef Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology. 2002;122:1035–47.PubMedCrossRef
31.
go back to reference Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.PubMedCrossRef Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.PubMedCrossRef
32.
go back to reference Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:71–8.PubMedCrossRef Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:71–8.PubMedCrossRef
33.
go back to reference Kawabata A, Kawao N, Kuroda R, Tanaka A, Shimada C. The PAR-1-activating peptide attenuates carrageenan-induced hyperalgesia in rats. Peptides. 2002;23:1181–3.PubMedCrossRef Kawabata A, Kawao N, Kuroda R, Tanaka A, Shimada C. The PAR-1-activating peptide attenuates carrageenan-induced hyperalgesia in rats. Peptides. 2002;23:1181–3.PubMedCrossRef
34.
go back to reference Fang M, Kovacs KJ, Fisher LL, Larson AA. Thrombin inhibits NMDA-mediated nociceptive activity in the mouse: possible mediation by endothelin. J Physiol. 2003;549:903–17.PubMedCrossRef Fang M, Kovacs KJ, Fisher LL, Larson AA. Thrombin inhibits NMDA-mediated nociceptive activity in the mouse: possible mediation by endothelin. J Physiol. 2003;549:903–17.PubMedCrossRef
35.
go back to reference Massi D, Naldini A, Ardinghi C, Carraro F, Franchi A, Paglierani M, et al. Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. Hum Pathol. 2005;36:676–85.PubMedCrossRef Massi D, Naldini A, Ardinghi C, Carraro F, Franchi A, Paglierani M, et al. Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. Hum Pathol. 2005;36:676–85.PubMedCrossRef
36.
go back to reference MacNaughton WK. Epithelial effects of proteinase-activated receptors in the gastrointestinal tract. Mem Inst Oswaldo Cruz. 2005;100(Suppl 1):211–5.PubMed MacNaughton WK. Epithelial effects of proteinase-activated receptors in the gastrointestinal tract. Mem Inst Oswaldo Cruz. 2005;100(Suppl 1):211–5.PubMed
Metadata
Title
Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients
Authors
Zhao Xiang Bian
Zhi Li
Zhi Xin Huang
Man Zhang
Hong Li Chen
Hong Xi Xu
Joseph J. Y. Sung
Publication date
01-07-2009
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 7/2009
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-009-0058-2

Other articles of this Issue 7/2009

Journal of Gastroenterology 7/2009 Go to the issue

Original Article—Liver, Pancreas, and Biliary Tract

Diagnostic utility of biopsy specimens for autoimmune pancreatitis

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.