title: Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon.
abstract: 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.
authors.affiliation: 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
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
authors.forename: Derrick
authors.initials: D
authors.lastname: Yates
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
authors.forename: Maria
authors.initials: M
authors.lastname: Vicario
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Mary H
authors.initials: MH
authors.lastname: Perdue
mesh_terms: 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
chemical_list: 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