title: Endogenous CRF in rat large intestine mediates motor and secretory responses to stress.
abstract: BACKGROUND
  Corticotropin-releasing factor (CRF) mediates our body's overall responses to stress. The role of central CRF in stress-stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress-induced colonic motor and secretory responses.
  
  
  METHODS
  Sprague-Dawley rats (adult, male) were subjected to 1-h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24 h. CRF mRNA and peptide levels in the colon were quantified by real-time RT-PCR, enzyme immuno-assay and immunohistochemistry. Double-stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference-mediated inhibition of CRF mRNA expression. DsRNA for β-globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1-h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance.
  
  
  RESULTS
  Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS-induced increase in CRF expression, whereas CRF expression in dsControl-injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS-induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance.
  
  
  CONCLUSIONS
  These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.
authors.affiliation: Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Ob-Gyn and Surgery, The Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Long
authors.affiliation: Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Beckwith
authors.affiliation: Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Talhouarne
authors.affiliation: Department of Ob-Gyn and Surgery, The Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Brooks
authors.affiliation: Departments of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: M-H
authors.initials: MH
authors.lastname: Qu
authors.affiliation: Departments of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ren
authors.affiliation: Departments of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wood
authors.affiliation: Department of Biology, College of Science and Health, University of Wisconsin-La Crosse, La Crosse, WI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Department of Ob-Gyn and Surgery, The Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bhargava
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005769:Gastrointestinal Motility / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism
chemical_list: D003346:Corticotropin-Releasing Hormone
keywords: CRF; colon; ion secretion; motility; stress