Peripheral corticotropin-releasing factor induces diarrhea in rats: role of CRF1 receptor in fecal watery excretion.
Systemic injection of corticotropin-releasing factor (CRF) stimulates colonic secretory and motor functions, and CRF receptors play a role in stress-related alterations of colonic functions. Stress has also been reported to induce diarrhea and we investigated if peripheral injection of CRF can mimic this response in conscious rats. Intravenous (i.v.) injection of CRF (3, 10 or 30 microg/kg) caused diarrhea in 13%, 63% and 75% of rats, respectively, and dose dependently increased the fecal fluid content by 5.1-, 8.6- and 10.8-fold, while the dried solid weight was increased by 5.2-, 4.9- and 5.8-fold, respectively, compared to the i.v. saline group. CRF actions were rapid in onset and blocked by the CRF1 receptor, antagonist CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine). These results demonstrate that peripheral CRF induces watery diarrhea, primarily through the activation of CRF1 receptor suggesting a possible role for these pathways in colonic responses to stress.
Saunders
Paul R
PR
Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, CURE, Department of Medicine, Digestive Diseases Division and Brain Research Institute, University of California, Los Angeles, CA 90073, USA. psaunder@ucla.edu
Maillot
Céline
C
Million
Mulugetta
M
Taché
Yvette
Y
D000704:Analysis of Variance; D000818:Animals; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000009:adverse effects* / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone