| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1
1Correspondence: Mucosal Inflammation Research Group, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada. E-mail: wmacnaug{at}ucalgary.ca
Proteinase-activated receptor 1 (PAR-1) is activated by thrombin and induces chloride secretion by intestinal epithelial cells. To elucidate further the mechanisms whereby PAR-1 stimulates secretion, monolayers of SCBN intestinal epithelial cells were studied in modified Ussing chambers. Short circuit current responses were determined after basolateral application of thrombin and the PAR-1-activating peptide, Ala-parafluoro-Phe-Arg-cyclohexyl-Ala-Citrulline-Tyr (Cit-NH2) in the presence or absence of a variety of signal transduction and cyclo-oxygenase (COX) pathway inhibitors. Increased kinase activity was monitored by immunoprecipitation and Western blot analysis of target phosphoproteins. The PAR-1-induced chloride secretory response was significantly attenuated by inhibitors of the EGF receptor tyrosine kinase, Src-kinase, MEK1/2, as well as by inhibitors of cytosolic phospholipase (cPL) A2, COX-1 and COX-2. PAR-1-induced activation of cPLA2, as shown by Western blot of phosphoserine residues, was blocked in cells treated with the MEK inhibitor U0126, indicating that the MEK-ERK1/2 MAP kinase pathway mediated PAR-1-induced cPLA2 phosphorylation. Our data show that PAR-1-induced chloride secretion in SCBN cells involves Src, EGF receptor trans-activation, activation of a MAPK pathway, phosphorylation of cPLA2, COX activity, but not PGF2
or PGE2. These findings may be of clinical importance in inflammatory diseases of the intestine where secretory dysfunction is evident and thrombin levels are elevated.—Buresi, M. C., Buret, A. G., Hollenberg, M. D., MacNaughton, W. K. Activation of proteinase-activated receptor 1 stimulates epithelial chloride secretion through a unique MAP kinase- and cyclo-oxygenase-dependent pathway.
Key Words: epidermal growth factor • PAR-1 • inflammatory bowel disease • PCR
This article has been cited by other articles:
|
|
 |
|
  A. C. Chin, W. Y. Lee, A. Nusrat, N. Vergnolle, and C. A. Parkos Neutrophil-mediated Activation of Epithelial Protease-Activated Receptors-1 and -2 Regulates Barrier Function and Transepithelial Migration J. Immunol., October 15, 2008; 181(8): 5702 - 5710. [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]
|
|
|
|
 |
|
 A. Smith, C. Contreras, K. H. Ko, J. Chow, X. Dong, B. Tuo, H.-h. Zhang, D.-b. Chen, and H. Dong Gender-Specific Protection of Estrogen against Gastric Acid-Induced Duodenal Injury: Stimulation of Duodenal Mucosal Bicarbonate Secretion Endocrinology, September 1, 2008; 149(9): 4554 - 4566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Teitelbaum, M. G. Gareau, J. Jury, P. C. Yang, and M. H. Perdue Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G452 - G459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Q. van der Merwe, M. D. Hollenberg, and W. K. MacNaughton EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G441 - G451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Kirkland, G. S. Cottrell, N. W. Bunnett, and C. U. Corvera Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G335 - G346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-F. Wang and G. I. Hatton Dominant Role of {beta}{gamma} Subunits of G-Proteins in Oxytocin-Evoked Burst Firing J. Neurosci., February 21, 2007; 27(8): 1902 - 1912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Balzary and T. M. Cocks Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2 J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 806 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kawao, M. Nagataki, K. Nagasawa, S. Kubo, K. Cushing, T. Wada, F. Sekiguchi, S. Ichida, M. D. Hollenberg, W. K. MacNaughton, et al. Signal Transduction for Proteinase-Activated Receptor-2-Triggered Prostaglandin E2 Formation in Human Lung Epithelial Cells J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 576 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Skinn and W. K. MacNaughton Nitric oxide inhibits cAMP-dependent CFTR trafficking in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G739 - G744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zhao, M. Morimoto, H. Dawson, J. E. Elfrey, K. B. Madden, W. C. Gause, B. Min, F. D. Finkelman, J. F. Urban Jr, and T. Shea-Donohue Immune Regulation of Protease-Activated Receptor-1 Expression in Murine Small Intestine during Nippostrongylus brasiliensis Infection J. Immunol., August 15, 2005; 175(4): 2563 - 2569. [Abstract] [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]
|
|
|
|
|
|
M. C. Buresi, N. Vergnolle, K. A. Sharkey, C. M. Keenan, P. Andrade-Gordon, G. Cirino, D. Cirillo, M. D. Hollenberg, and W. K. MacNaughton Activation of proteinase-activated receptor-1 inhibits neurally evoked chloride secretion in the mouse colon in vitro Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G337 - G345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kawabata, S. Kubo, T. Ishiki, N. Kawao, F. Sekiguchi, R. Kuroda, M. D. Hollenberg, T. Kanke, and N. Saito Proteinase-Activated Receptor-2-Mediated Relaxation in Mouse Tracheal and Bronchial Smooth Muscle: Signal Transduction Mechanisms and Distinct Agonist Sensitivity J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 402 - 410. [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]
|
|
|
|
 |
|
 A. C. Chin, N. Vergnolle, W. K. MacNaughton, J. L. Wallace, M. D. Hollenberg, and A. G. Buret Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability PNAS, September 16, 2003; 100(19): 11104 - 11109. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
