Regulation of Cl- permeability in normal and cystic fibrosis sweat duct cells.
Reabsorptive cells of the human sweat gland normally exhibit a high basal Cl- permeability but are markedly impermeable to Cl- in cystic fibrosis (CF). We examined the possibility that the reduced basal Cl- permeability of CF sweat duct cells in primary culture is due to a defective regulation of plasma membrane Cl- permeability by prostaglandin E2 (PGE2), which is endogenously produced by cultured sweat duct cells. The macroscopic Cl- permeabilities of normal and CF sweat duct cells were assessed using a halide-specific fluorescent dye, 6-methoxy-N-(3-sulfopropyl)quinolinium, in combination with fluorescence digital-imaging microscopy. The Cl- and Br- permeabilities of normal sweat duct cells were markedly reduced by inhibiting endogenous PGE2 production with indomethacin. This inhibition of Cl- permeability by indomethacin was largely reversed by the addition of PGE2 (10 nM to 1 microM), but not forskolin. Conversely, PGE2 failed to stimulate the low Cl- permeabilities of sweat duct cells cultured from CF subjects. Our results support the following conclusions: 1) a defective regulation of Cl- permeability in CF is a feature of reabsorptive as well as secretory epithelial cells, and 2) the nature of this regulatory defect extends beyond altered Cl- permeability regulation by adenosine 3',5'-cyclic monophosphate-dependent protein kinase.
Ram
S J
SJ
Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham 35294.
Weaver
M L
ML
Kirk
K L
KL
D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D012016:Reference Values; D013545:Sweat Glands / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*
D002712:Chlorides; D015232:Dinoprostone; D007213:Indomethacin