Acute stress increases colonic paracellular permeability in mice through a mast cell-independent mechanism: involvement of pancreatic trypsin.
OBJECTIVE
Increased colonic paracellular permeability (CPP) is a key feature of gastro-intestinal disorders as irritable bowel syndrome and inflammatory bowel diseases. Stress stimulates exocrine pancreatic secretion through cholinergic pathways, and trypsin is known to increase CPP. Consequently we have investigated in this work whether trypsin released into the gut lumen following an acute stress may participate to the short-term increase in CPP.


METHODS
Mice were treated with atropine or a non-selective CRF (corticotropin-releasing factor) receptor antagonist (alpha-helical CRF (9-41)), before being submitted to a 2-h stress session. Then, CPP and protease activity in colonic contents (total proteolytic, trypsin activity, and mouse mast cell protease (MMCP)-1 levels) were determined. The effects of colonic contents from sham-stressed or stressed animals on CPP were evaluated in mice colonic tissues mounted in Ussing chambers, in presence or not of soybean trypsin inhibitor (SBTI) or FSLLRY, a protease-activated receptor-2 (PAR2) antagonist.


RESULTS
Acute stress significantly increased CPP, proteolytic and trypsin activities, and MMCP-1 levels. Atropine inhibited stress-induced impairment of CPP and strongly diminished total proteolytic and trypsin activities in stressed animals, but not MMCP-1 levels. Colonic contents from stressed animals increased CPP in mice tissues, this effect being inhibited by SBTI and PAR2 antagonist.


CONCLUSIONS
Acute stress activates cholinergic pathways, to trigger exocrine pancreatic secretion. Trypsin, released in these conditions, may be responsible for colonic barrier alterations through the activation of PAR2.
Demaude
Julien
J
INRA, EI-Purpan, UMR 1054 Neuro-Gastroenterology & Nutrition, F-31000 Toulouse, France.
Levêque
Mathilde
M
Chaumaz
Gilles
G
Eutamène
Hélène
H
Fioramonti
Jean
J
Bueno
Lionel
L
Ferrier
Laurent
L
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D003106:Colon / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D010179:Pancreas / Q000201:enzymology*; D013315:Stress, Psychological / Q000201:enzymology* / Q000473:pathology; D014357:Trypsin / Q000378:metabolism / Q000502:physiology*
D014357:Trypsin