title: Residual chloride secretion in intestinal tissue of deltaF508 homozygous twins and siblings with cystic fibrosis. The European CF Twin and Sibling Study Consortium.
abstract: OBJECTIVE
  Cholinergic stimulation of chloride secretion is impaired in the intestines of patients with cystic fibrosis (CF). However, intestinal chloride secretion has been observed in patients with mild CF mutations. The aim of this study was to investigate residual Cl(-) secretion in the intestine of DeltaF508 homozygous CF patients, and examine the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) and alternative Cl(-) conductances. Twins and siblings with identical CFTR genotypes were investigated to determine the impact of factors other than CFTR on chloride secretion.
  
  
  METHODS
  Chloride secretion in rectal tissue was investigated by applying Ca(2+) and adenosine 3',5'-cyclic monophosphate (cAMP)-linked agonists before and after the inhibition of alternative Cl(-) conductances with 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS).
  
  
  RESULTS
  cAMP-mediated Cl(-) secretion was observed in 73% of patients, and 20% showed DIDS-sensitive Ca(2+)-activated Cl(-) secretion. This DIDS-sensitive alternative chloride conductance was seen only in CF patients who also responded to cAMP agonists. Chloride secretion was more concordant within monozygous twins than within dizygous pairs.
  
  
  CONCLUSIONS
  These results suggest the presence of CFTR-mediated Cl(-) secretion in a subgroup of patients, implying that a portion of deltaF508 CFTR can be processed in vivo and function as a chloride channel in the apical membrane of intestinal cells. Moreover, a considerable number of deltaF508 homozygous patients express chloride conductances other than CFTR in their intestinal epithelia.
authors.affiliation: Department of Pediatrics, Sophia Children's Hospital, Rotterdam, The Netherlands. bronsvel@worldonline.nl
authors.forename: I
authors.initials: I
authors.lastname: Bronsveld
authors.forename: F
authors.initials: F
authors.lastname: Mekus
authors.forename: J
authors.initials: J
authors.lastname: Bijman
authors.forename: M
authors.initials: M
authors.lastname: Ballmann
authors.forename: J
authors.initials: J
authors.lastname: Greipel
authors.forename: J
authors.initials: J
authors.lastname: Hundrieser
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
authors.forename: U
authors.initials: U
authors.lastname: Laabs
authors.forename: R
authors.initials: R
authors.lastname: Busche
authors.forename: H R
authors.initials: HR
authors.lastname: De Jonge
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
authors.forename: H J
authors.initials: HJ
authors.lastname: Veeze
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000819:agonists / Q000502:physiology; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004200:Diseases in Twins; D004594:Electrophysiology; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D012007:Rectum / Q000378:metabolism* / Q000503:physiopathology; D012016:Reference Values; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid