title: Up-regulated cystic fibrosis transmembrane conductance regulator after anal stenosis in rats.
abstract: BACKGROUND
  The pathophysiology of fecal incontinence from fecal impaction and rectal distension is poorly understood. We hypothesize that fecal impaction elicits up-regulation of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated mucosal chloride channel.
  
  
  METHODS
  The anus was ligated to produce 75% stenosis in rats. Controls received ligation without inducing stenosis. 24 to 48 hours after ligation the colon was removed. Mucosal short-circuit current was measured by Ussing chamber. Western blot analysis was used to detect CFTR expression in the colonic mucosa. Ligated rats failed to defecate, whereas control rats stooled normally.
  
  
  RESULTS
  Ligated colons were markedly stool filled and dilated. Water content of feces was significantly increased to 66.5% ± 1.1% (P < .01, n = 12) 24 hours after ligation, vs controls (49.5 ± 5.2%, n = 12). Baseline short-circuit current was significantly increased in the distal (78.8 ± 7.4 μA/cm(2), n = 8, P < .01) and mid colon (24.5 ± 2.5 μA/cm(2), n = 8, P < .05) 24 hours after ligation, compared to control rats (12.5 ± 3.2 μA/cm2, n = 8). CFTR expression was significantly increased 24 hours after ligation in the mid and distal colon.
  
  
  CONCLUSIONS
  We observe that fecal impaction from anal ligation induces early compensatory up-regulation of CFTR, altering function from net absorption to net secretion in the mid and distal colon.
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI 53295, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ramprasad
authors.forename: Manu
authors.initials: M
authors.lastname: Sood
authors.forename: Kirk
authors.initials: K
authors.lastname: Ludwig
authors.forename: Toku
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D001003:Anal Canal / Q000601:surgery; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D005244:Fecal Impaction / Q000378:metabolism* / Q000503:physiopathology; D005242:Fecal Incontinence / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000503:physiopathology; D008026:Ligation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator