Activation of ion secretion via proteinase-activated receptor-2 in human colon

Mall, M., Gonska, T., Thomas, J., Hirtz, S., Schreiber, R. and Kunzelmann, K. (2002) Activation of ion secretion via proteinase-activated receptor-2 in human colon. American Journal of Physiology-gastrointestinal And Liver Physiology, 282 2: G200-G210.


Author Mall, M.
Gonska, T.
Thomas, J.
Hirtz, S.
Schreiber, R.
Kunzelmann, K.
Title Activation of ion secretion via proteinase-activated receptor-2 in human colon
Journal name American Journal of Physiology-gastrointestinal And Liver Physiology   Check publisher's open access policy
Publication date 2002
Sub-type Article
DOI 10.1152/ajpgi.00137.2001
Volume number 282
Issue number 2
ISSN 0193-1857
Start page G200
End page G210
Total pages 10
Editor M. F. Kagnoff
Brenda B. Rauner
Place of publication USA
Publisher American Physiological Society
Collection year 2002
Language eng
Subject C1
270104 Membrane Biology
780105 Biological sciences
Abstract Proteinase-activated receptor (PAR) type 2 (PAR-2) has been shown to mediate ion secretion in cultured epithelial cells and rat jejunum. With the use of a microUssing chamber, we demonstrate the role of PAR-2 for ion transport in native human colonic mucosa obtained from 30 normal individuals and 11 cystic fibrosis (CF) patients. Trypsin induced Cl- secretion when added to the basolateral but not luminal side of normal epithelia. Activation of Cl- secretion by trypsin was inhibited by indomethacin and was further increased by cAMP in normal tissues but was not present in CF colon, indicating the requirement of luminal CF transmembrane conductance regulator. Effects of trypsin were largely reduced by low Cl-,by basolateral bumetanide, and in the presence of barium or clotrimazole, but not by tetrodotoxin. Furthermore, trypsin-induced secretion was inhibited by the Ca2+-ATPase inhibitor cyclopiazonic acid and in low-Ca2+ buffer. The effects of trypsin were almost abolished by trypsin inhibitor. Thrombin, an activator of PAR types 1, 3, and 4, had no effects on equivalent short-circuit currents. The presence of PAR-2 in human colon epithelium was confirmed by RT-PCR and additional experiments with PAR-2-activating peptide. PAR-2-mediated intestinal electrolyte secretion by release of mast cell tryptase and potentiation of PAR-2 expression by tumor necrosis factor-alpha may contribute to the hypersecretion observed in inflammatory processes such as chronic inflammatory bowel disease.
Keyword Gastroenterology & Hepatology
Physiology
Protease-activated Receptors
Ion Transport
Trypsin
Cystic Fibrosis Transmembrane Conductance Regulator
Inflammatory Bowel Disease
Inflammatory Bowel-disease
Necrosis-factor-alpha
Cystic-fibrosis
Antibody Infliximab
Molecular-cloning
Crohns-disease
Mast-cells
Transport
Channels
Biopsies
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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