Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.
We examined the effect of stress on colonic epithelial physiology, the role of corticotropin-releasing hormone (CRH), and the pathways involved. Rats were restrained or injected intraperitoneally with CRH or saline. Colonic segments were mounted in Ussing chambers, in which ion secretion and permeability (conductance and probe fluxes) were measured. To test the pathways involved in CRH-induced changes, rats were pretreated with hexamethonium, atropine, bretylium, doxantrazole, alpha-helical CRH-(9-41) (all intraperitoneally), or aminoglutethimide (subcutaneously). Restraint stress increased colonic ion secretion and permeability to ions, the bacterial peptide FMLP, and horseradish peroxidase (HRP). These changes were prevented by alpha-helical CRH-(9-41) and mimicked by CRH (50 microgram/kg). CRH-induced changes in ion secretion were abolished by alpha-helical CRH-(9-41), hexamethonium, atropine, or doxantrazole. CRH-stimulated conductance was significantly inhibited by alpha-helical CRH-(9-41), hexamethonium, bretylium, or doxantrazole. CRH-induced enhancement of HRP flux was significantly reduced by all drugs but aminoglutethimide. Peripheral CRH reproduced stress-induced colonic epithelial pathophysiology via cholinergic and adrenergic nerves and mast cells. Modulation of stress responses may be relevant to the management of colonic disorders.
Santos
J
J
Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Saunders
P R
PR
Hanssen
N P
NP
Yang
P C
PC
Yates
D
D
Groot
J A
JA
Perdue
M H
MH
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001949:Bretylium Compounds / Q000494:pharmacology; D003106:Colon / Q000378:metabolism / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D004553:Electric Conductivity; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013312:Stress, Physiological / Q000503:physiopathology*
D001949:Bretylium Compounds; D006727:Hormone Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D018738:Hexamethonium; D001285:Atropine; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D006735:Horseradish Peroxidase; C045166:bretylium