X-RAY-MICROANALYSIS OF CELL ELEMENTS IN NORMAL AND CYSTIC-FIBROSIS JEJUNUM - EVIDENCE FOR CHLORIDE SECRETION IN VILLI

Background di Aims: Cystic fibrosis transmembrane conductance regulato r (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 intest ine of patients with cystic fibrosis alters the intracellular electrol yte 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 avai lable antibodies, Results: Cystic fibuosis jejunum had a significantly lower Na+ content, higher K+ and Cl- content, and higher potassium/ph osphorus ratio in both villus and crypt regions. Incubation of normal jejunum with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthi ne (300 mu mol/L) resulted in decreased K+ and Cl- content in both cry pt and villus regions, indicative of Cl- secretion, CFTR was identifie d on the surface of normal villus and crypt enterocytes but not in cys tic fibrosis samples, Conclusions: Defective apical chloride channels in cystic fibrosis result in alterations in the intracellular electrol yte milieu, The microanalysis observations and immunocytochemical stud ies imply a role for villus enterocytes in human intestinal chloride s ecretion.