| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, Toulouse, France;
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and
Department of Surgery and Physiology, University of California, San Francisco, CA 94143
Activation of colonic proteinase-activated receptor-2 (PAR-2) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is under debate and could be neurogenic and/or the consequence of tight-junction opening with passage of exogenous pathogens into the lamina propria. The present study aimed to further characterize the inflammatory effect of PAR-2 activation by investigating: 1) the role of NO, 2) the role of afferent neurons, and 3) a possible cause and effect relationship between colonic paracellular permeability changes and mucosal inflammation. Thus, intracolonic infusion to mice of the PAR-2-activating peptide, SLIGRL, increased both myeloperoxidase (MPO) activity and damage scores indicating colonic inflammation, and enhanced colonic permeability to 51Cr-EDTA from 2 to 4 h after its infusion. NO synthase inhibitors, L-NAME and aminoguanidine, as well as the neurotoxin capsaicin and NK1, calcitonin gene-related peptide (CGRP) receptor antagonists, SR140333 and CGRP8–37, prevented SLIGRL-induced MPO and damage score increases and permeability. In contrast, although the tight-junction blocker, 2,4,6-triaminopyrimidine, and the myosin L chain kinase inhibitor, ML-7, prevented SLIGRL-induced increase in permeability, they did not prevent MPO and damage score increases. Taken together our data show that both NO and capsaicin-sensitive afferent neurons are involved in PAR-2-mediated colonic inflammation and paracellular permeability increase. Nevertheless, the inflammation process is not a consequence of increased permeability which results at least in part from the activation of myosin L chain kinase.
This article has been cited by other articles:
|
|
 |
|
  Z.-Y. Wang, P. Wang, and D. E. Bjorling Role of mast cells and protease-activated receptor-2 in cyclooxygenase-2 expression in urothelial cells Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R1127 - R1135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Sutton, A. Zhao, K. B. Madden, J. E. Elfrey, B. A. Tuft, C. A. Sullivan, J. F. Urban Jr., and T. Shea-Donohue Anti-Inflammatory Mechanisms of Enteric Heligmosomoides polygyrus Infection against Trinitrobenzene Sulfonic Acid-Induced Colitis in a Murine Model Infect. Immun., October 1, 2008; 76(10): 4772 - 4782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Hyun, P Andrade-Gordon, M Steinhoff, and N Vergnolle Protease-activated receptor-2 activation: a major actor in intestinal inflammation Gut, September 1, 2008; 57(9): 1222 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. B. Sipe, S. M. Brierley, C. M. Martin, B. D. Phillis, F. B. Cruz, E. F. Grady, W. Liedtke, D. M. Cohen, S. Vanner, L. A. Blackshaw, et al. Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1288 - G1298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Knecht, G. S. Cottrell, S. Amadesi, J. Mohlin, A. Skaregarde, K. Gedda, A. Peterson, K. Chapman, M. D. Hollenberg, N. Vergnolle, et al. Trypsin IV or Mesotrypsin and p23 Cleave Protease-activated Receptors 1 and 2 to Induce Inflammation and Hyperalgesia J. Biol. Chem., September 7, 2007; 282(36): 26089 - 26100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Moussa, J. Apostolopoulos, P. Davenport, J. Tchongue, and P. G. Tipping Protease-Activated Receptor-2 Augments Experimental Crescentic Glomerulonephritis Am. J. Pathol., September 1, 2007; 171(3): 800 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Roka, A. Ait-Belgnaoui, C. Salvador-Cartier, R. Garcia-Villar, J. Fioramonti, H. Eutamene, and L. Bueno Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats Gut, August 1, 2007; 56(8): 1072 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zoudilova, P. Kumar, L. Ge, P. Wang, G. M. Bokoch, and K. A. DeFea beta-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2 J. Biol. Chem., July 13, 2007; 282(28): 20634 - 20646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Grant, G. S. Cottrell, S. Amadesi, M. Trevisani, P. Nicoletti, S. Materazzi, C. Altier, N. Cenac, G. W. Zamponi, F. Bautista-Cruz, et al. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice J. Physiol., February 1, 2007; 578(3): 715 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Amadesi, G. S. Cottrell, L. Divino, K. Chapman, E. F. Grady, F. Bautista, R. Karanjia, C. Barajas-Lopez, S. Vanner, N. Vergnolle, et al. Protease-activated receptor 2 sensitizes TRPV1 by protein kinase C{varepsilon}- and A-dependent mechanisms in rats and mice J. Physiol., September 1, 2006; 575(2): 555 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cattaruzza, N. Cenac, E. Barocelli, M. Impicciatore, E. Hyun, N. Vergnolle, and C. Sternini Protective Effect of Proteinase-Activated Receptor 2 Activation on Motility Impairment and Tissue Damage Induced by Intestinal Ischemia/Reperfusion in Rodents Am. J. Pathol., July 1, 2006; 169(1): 177 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Moriez, C. Salvador-Cartier, V. Theodorou, J. Fioramonti, H. Eutamene, and L. Bueno Myosin Light Chain Kinase Is Involved in Lipopolysaccharide-Induced Disruption of Colonic Epithelial Barrier and Bacterial Translocation in Rats Am. J. Pathol., October 1, 2005; 167(4): 1071 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jacob, P.-C. Yang, D. Darmoul, S. Amadesi, T. Saito, G. S. Cottrell, A.-M. Coelho, P. Singh, E. F. Grady, M. Perdue, et al. Mast Cell Tryptase Controls Paracellular Permeability of the Intestine: ROLE OF PROTEASE-ACTIVATED RECEPTOR 2 AND {beta}-ARRESTINS J. Biol. Chem., September 9, 2005; 280(36): 31936 - 31948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Hansen, P. M. Sherman, L. Cellars, P. Andrade-Gordon, Z. Pan, A. Baruch, J. L. Wallace, M. D. Hollenberg, and N. Vergnolle A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis PNAS, June 7, 2005; 102(23): 8363 - 8368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Vergnolle CLINICAL RELEVANCE OF PROTEINASE ACTIVATED RECEPTORS (PARS) IN THE GUT Gut, June 1, 2005; 54(6): 867 - 874. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cenac, A. C. Chin, R. Garcia-Villar, C. Salvador-Cartier, L. Ferrier, N. Vergnolle, A. G. Buret, J. Fioramonti, and L. Bueno PAR2 activation alters colonic paracellular permeability in mice via IFN-{gamma}-dependent and -independent pathways J. Physiol., August 1, 2004; 558(3): 913 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Amadesi, J. Nie, N. Vergnolle, G. S. Cottrell, E. F. Grady, M. Trevisani, C. Manni, P. Geppetti, J. A. McRoberts, H. Ennes, et al. Protease-Activated Receptor 2 Sensitizes the Capsaicin Receptor Transient Receptor Potential Vanilloid Receptor 1 to Induce Hyperalgesia J. Neurosci., May 5, 2004; 24(18): 4300 - 4312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. OSSOVSKAYA and N. W. BUNNETT Protease-Activated Receptors: Contribution to Physiology and Disease Physiol Rev, April 1, 2004; 84(2): 579 - 621. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
