Chloride Secretion Patterns In Rectal Epithelium Of Cystic-Fibrosis (Cf) Patients And Its Relation To The Delta-F508 Mutation

In CF the calcium-(Ca) and cAMP mediated regulation of the chloride channel are defective in small intestine and proximal colon. In order to demonstrate the defect in rectal epithelium we studied suction biopsies in a modified ussing chamber (exposed area 1. 13 mm2) in 20 CF patients and 17 controls. Ca-mediated change in short circuit current (SCC) by Carbachol, positively associated with chloride secretion, was measured. The change in SCC ± S. E. M. (n) was +24. 5 ± 3.1 (17) in controls and -9.9 ± 2.6 (12) in CF (category I). Eight CF patients (including 3 sibs) showed a positive peak change in SCC of +4.8 ± 2.3 indicating residual chloride secretion after the initial response of -5.2 ± 1.8 (category II). Homozygosity for the most common CF mutation (ΔF508) was found exclusively in category I (n=6). Compound heterozygosity (ΔF508 and another unknown mutation) was seen in 2 patients of category I and in all patients tested (n=6) for category II. CF patients with residual chloride secretion tend to have better lungfunctions and less disturbed sweat tests, not to be explained by differences in age. Reverse response in CF is a consistent and intriguing finding and represents a possible potassium secretion CONCLUSIONS: CF rectal epithelium of homozygotes for ΔF508 showed an absent Ca-mediated chloride secretion corresponding with earlier studies of small intestine and proximal colon. One third of the CF patients however showed residual chloride secretion; these patients were heterozygotes for ΔF508. In 2 compound heterozygotes without residual chloride secretion we suggest that the other mutation is of the same severity as ΔF508.