Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat.
BACKGROUND A 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. METHODS This 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 RESULTS No 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 & INFERENCES This 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.
o'malley
D
D
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Julio-Pieper
M
M
Gibney
S M
SM
Gosselin
R D
RD
Dinan
T G
TG
Cryan
J F
JF
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D003106:Colon / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008297:Male; D009043:Motor Activity / Q000502:physiology; D010146:Pain / Q000378:metabolism*; D010812:Physical Stimulation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D013037:Spatial Behavior / Q000502:physiology; D013045:Species Specificity; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone