X-ray microanalysis of cell elements in normal and cystic fibrosis jejunum: Evidence for chloride secretion in villi

doi:10.1053/gast.1996.v110.pm8566587

Gastroenterology

Volume 110, Issue 2, February 1996, Pages 411-418

https://doi.org/10.1053/gast.1996.v110.pm8566587 Get rights and content

Abstract

BACKGROUND & AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) is an adenosine 3',5'-cyclic monophosphate-dependent chloride channel that is defective in cystic fibrosis. The aims of this study were to determine if defective apical chloride secretion in the intestine of patients with cystic fibrosis alters the intracellular electrolyte milieu and to examine the geographical localization of CFTR in the normal intestine. METHODS: The content of intracellular elements was assessed in cryosections using energy-dispersive x-ray microanalysis, and CFTR was identified by immunocytochemistry using commercially available antibodies. RESULTS: Cystic fibrosis jejunum had a significantly lower Na+ content, higher K+ and Cl- content, and higher potassium/phosphorus ratio in both villus and crypt regions. Incubation of normal jejunum with the phosphodiesterase inhibitor 3- isobutyl-1-methyl-xanthine (300 mumol/L) resulted in decreased K+ and Cl- content in both crypt and villus regions, indicative of Cl- secretion. CFTR was identified on the surface of normal villus and crypt enterocytes but not in cystic fibrosis samples. CONCLUSIONS: Defective apical chloride channels in cystic fibrosis result in alterations in the intracellular electrolyte milieu. The microanalysis observations and immunocytochemical studies imply a role for villus enterocytes in human intestinal chloride secretion. (Gastroenterology 1996 Feb;110(2):411-8)

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Through subsequent studies, as described above (Epithelial Ion and Fluid secretion) the molecular mechanisms and transporters underlying cAMP dependent Cl secretion were identified. Although by no means universally accepted, there are models that best seem to fit the available data regarding intestinal fluid transport (Kockerling & Fromm, 1993; O'Loughlin et al., 1996). In such models, in the small intestine, most (but possibly not all) secretion arises from the crypts, whereas all absorption occurs in the villi.
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