The role of rectal chloride secretion in childhood constipation

Neurogastroenterol Motil. 2011 Nov;23(11):1007-12. doi: 10.1111/j.1365-2982.2011.01751.x. Epub 2011 Aug 17.

Abstract

Background: Disturbance in fluid secretion, driven by chloride secretion, might play a role in constipation. However, disturbed chloride secretion in those patients has yet to be evaluated. Therefore, the aim of this study was to compare chloride secretion in rectal biopsies of children with functional constipation (FC) to those without constipation.

Methods: To measure changes in short circuit current (I(sc) in μA cm(-2)) reflecting chloride secretion, intestinal biopsies from children with constipation, to either exclude or diagnose Hirschsprung's disease, and from children without constipation (controls) undergoing colonoscopy for screening of familial adenomatous polyposis, juvenile polyps or inflammatory bowel disease (IBD), were compared and studied in Ussing chambers. Following electrogenic sodium absorption blockade by amiloride, chloride secretory responses to calcium-linked (histamine, carbachol) and cAMP-linked (IBMX/forskolin) secretagogues were assessed.

Key results: Ninety-six patients (46 FC) participated; nine FC patients (n = 1 congenital syndrome and n = 8 technical problems) and 13 controls (n = 6 IBD; n = 7 technical problems) were excluded. No significant difference was found in mean (±SE) basal chloride currents between children with FC and controls (9.6 ± 1.1 vs 9.2 ± 0.8; P = 0.75, respectively). Responses to calcium-linked chloride secretagogues (histamine and carbachol) were significantly higher in controls (33.0 ± 3.0 vs 24.5 ± 2.3; P = 0.03 and 33.6 ± 3.4 vs 26.4 ± 2.7; P = 0.05 following histamine and carbachol, respectively).

Conclusions & inferences: Calcium-linked chloride secretion is disturbed in children with FC. Whether this defect occurs at the level of histamine receptors, components of receptor-linked signal transduction pathways or basolateral Ca(2+) -sensitive K(+) channels enhancing the electrical driving force for apical chloride secretion, remains to be explored.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / metabolism
  • Amiloride / metabolism
  • Biopsy
  • Carbachol / metabolism
  • Child
  • Chlorides / metabolism*
  • Cholinergic Agonists / metabolism
  • Colforsin / metabolism
  • Constipation / diagnosis
  • Constipation / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Defecation
  • Female
  • Hirschsprung Disease / diagnosis
  • Hirschsprung Disease / physiopathology
  • Histamine / metabolism
  • Histamine Agonists / metabolism
  • Humans
  • Male
  • Phosphodiesterase Inhibitors / metabolism
  • Rectum / metabolism*
  • Rectum / surgery
  • Sodium Channel Blockers / metabolism

Substances

  • CFTR protein, human
  • Chlorides
  • Cholinergic Agonists
  • Histamine Agonists
  • Phosphodiesterase Inhibitors
  • Sodium Channel Blockers
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin
  • Amiloride
  • Histamine
  • Carbachol
  • 1-Methyl-3-isobutylxanthine