Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon.
BACKGROUND
Previously, we showed that corticotropin-releasing factor (CRF) injected i.p. mimicked epithelial responses to stress, both stimulating ion secretion and enhancing permeability in the rat colon, and mast cells were involved. However, the ability of CRF-sensitive mucosal/submucosal loops to regulate intestinal barrier and the participation of resident mast cells are unclear.


METHODS
We examined colonic epithelial responses to stress-like peptides in Wistar-Kyoto (WKY), and mast cell-deficient (Ws/Ws) and their +/+ littermate control rats in distal segments mounted in Ussing chambers. Short-circuit current (ion secretion), flux of horseradish peroxidase (macromolecular permeability), and the release of rat mast cell protease II were measured in response to CRF [10(-6) to 10(-8)M] or sauvagine [10(-8) to 10(-10)M] in tissues pretreated with astressin, doxantrazole, or vehicle.


RESULTS
Stress-like peptides (sauvagine > CRF) induced a dose-dependent increase in short-circuit current (maximal at 30 min), and significantly enhanced horseradish peroxidase flux and protease II release in WKY. Epithelial responses were inhibited by both astressin and doxantrazole, and significantly reduced in tissues from Ws/Ws rats.


CONCLUSIONS
The stress mediators CRF and sauvagine modulate barrier function in the rat colon acting on mucosal/submucosal CRF receptor-bearing cells, through mast cell-dependent pathways.
Santos
Javier
J
Digestive Diseases Research Unit, Institut de Recerça Vall d'Hebron, Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain. jsantos@ir.vhebron.net
Yates
Derrick
D
Guilarte
Mar
M
Vicario
Maria
M
Alonso
Carmen
C
Perdue
Mary H
MH
D029845:Amphibian Proteins / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D036361:Peptide Hormones / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D011922:Rats, Mutant Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000276:immunology*; D013892:Thioxanthenes / Q000008:administration & dosage; D044004:Xanthones / Q000008:administration & dosage
D029845:Amphibian Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D036361:Peptide Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; D013892:Thioxanthenes; D044004:Xanthones; C104416:astressin; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone; C010134:doxantrazole