title: The role of rectal chloride secretion in childhood constipation.
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.
  
  
  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
  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.
authors.affiliation: Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam, The Netherlands. n.bekkali@amc.nl
authors.forename: N
authors.initials: N
authors.lastname: Bekkali
authors.forename: H R
authors.initials: HR
authors.lastname: de Jonge
authors.forename: R M J G J
authors.initials: RM
authors.lastname: van den Wijngaard
authors.forename: A F W
authors.initials: AF
authors.lastname: van der Steeg
authors.forename: P B
authors.initials: PB
authors.lastname: Bijlsma
authors.forename: J A J M
authors.initials: JA
authors.lastname: Taminiau
authors.forename: J F
authors.initials: JF
authors.lastname: Desjeux
authors.forename: M A
authors.initials: MA
authors.lastname: Benninga
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000378:metabolism; D000584:Amiloride / Q000378:metabolism; D001706:Biopsy; D002217:Carbachol / Q000378:metabolism; D002648:Child; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D003248:Constipation / Q000175:diagnosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D003672:Defecation; D005260:Female; D006627:Hirschsprung Disease / Q000175:diagnosis / Q000503:physiopathology; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000378:metabolism; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D012007:Rectum / Q000378:metabolism* / Q000601:surgery; D026941:Sodium Channel Blockers / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D018679:Cholinergic Agonists; D017442:Histamine Agonists; D010726:Phosphodiesterase Inhibitors; D026941:Sodium Channel Blockers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000584:Amiloride; D006632:Histamine; D002217:Carbachol; D015056:1-Methyl-3-isobutylxanthine