Peer-Reviewed Journal Details
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O'Malley, D; Julio-Pieper, M; Gibney, SM; Gosselin, RD; Dinan, TG; Cryan, JF;
2010
January
Neurogastroenterology and Motility
Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat
Validated
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Optional Fields
brain-gut axis corticotropin-releasing factor receptors irritable bowel syndrome stress Wistar Kyoto IRRITABLE-BOWEL-SYNDROME INDUCED VISCERAL PAIN GUT MOTOR FUNCTION GASTROINTESTINAL-TRACT FACTOR CRF MATERNAL-DEPRIVATION EPITHELIAL RESPONSES MESSENGER-RNAS LIFE STRESS EXPRESSION
22
301
311
BackgroundA growing body of data implicates increased life stresses with the initiation, persistence and severity of symptoms associated with functional gut disorders such as irritable bowel syndrome (IBS). Activation of central and peripheral corticotropin-releasing factor (CRF) receptors is key to stress-induced changes in gastrointestinal (GI) function.MethodsThis study utilised immunofluorescent and Western blotting techniques to investigate colonic expression of CRF receptors in stress-sensitive Wistar Kyoto (WKY) and control Sprague Dawley (SD) rats.Key ResultsNo intra-strain differences were observed in the numbers of colonic CRFR1 and CRFR2 positive cells. Protein expression of functional CRFR1 was found to be comparable in control proximal and distal colon samples. Sham levels of CRFR1 were also similar in the proximal colon but significantly higher in WKY distal colons (SD: 0.38 +/- 0.14, WKY: 2.06 +/- 0.52, P < 0.01). Control levels of functional CRFR2 were similar between strains but sham WKYs samples had increased CRFR2 in both the proximal (SD: 0.88 +/- 0.21, WKY: 1.8 +/- 0.18, P < 0.001) and distal (SD: 0.18 +/- 0.08, WKY: 0.94 +/- 0.32, P < 0.05) regions. Exposure to open field (OF) and colorectal distension (CRD) stressors induced decreased protein expression of CRFR1 in SD proximal colons, an effect that was blunted in WKYs. CRD stimulated decreased expression of CRFR2 in WKY rats alone. Distally, CRFR1 is decreased in WKY rats following CRD but not OF stress without any apparent changes in SD rats.Conclusions & InferencesThis study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function.
DOI 10.1111/j.1365-2982.2009.01412.x
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