ABNORMAL EPITHELIAL TRANSPORT IN CYSTIC-FIBROSIS JEJUNUM

Abnormal epithelial electrolyte transport has been identified in a range of cystic fibrosis (CF) organs and appears to account for the various clinical manifestations of the disease. The aim of this study was to further define the Cl- secretion defect in CF jejunum. Excised jejunum was obtained from 11 CF patients and 12 controls. Transport studies were performed on stripped epithelium in vitro under short-circuited conditions in Ussing Chambers. 3-Isobutyl-1-methylxanthine (IBMX) (300-mu-M) significantly increased Cl- secretion in control (-2.3 +/- 0.6 to -3.3 +/- 0.7-mu-eq.cm-2.h-1; P < 0.01, paired t test; n = 5 subjects) but not in CF jejunum (-0.5 +/- 0.3 to -0.1 +/- 0.4; n = 4). However in contrast to control jejunum, net Na+ absorption in CF jejunum was higher in the IBMX (1.3 +/- 0.5 mu-eq.cm-2.h-1) compared with basal periods (0.6 +/- 0.3; P < 0.05, paired t test). IBMX stimulation of tissue adenosine 3',5'-cyclic monophosphate (cAMP) was similar in both control and CF jejunum. A range of secretagogues known to induce secretion in mammalian intestine, including dibutyryl cAMP (DBcAMP), DBcGMP, Ca2+ ionophore A23187, and the protein kinase C activator 4-beta-phorbol 12,13-dibutyrate, failed to induce secretion in CF jejunum. In conclusion, CF jejunum failed to exhibit Cl- secretion and also demonstrated abnormalities of Na+ absorption. These results support the view that the defect lies at a site distal to the intracellular messengers. Moreover, these abnormalities of intestinal electrolyte transport may account for some of the gastrointestinal manifestations of the disease such as meconium ileus and distal intestinal obstruction syndrome.