Altered fluid transport across airway epithelium in cystic fibrosis.
In cystic fibrosis (CF), absence or dysfunction of a phosphorylation-regulated chloride channel [CF transmembrane conductance regulator (CFTR)] leads to the loss or reduction of chloride secretion into the airways. Active sodium absorption is also increased in CF, and both of these ion transport changes could alter fluid transport across the airways. Under baseline conditions, cultured human airway epithelia from normal individuals absorbed fluid, and this absorption was increased in epithelia from patients with CF. In normal and CF epithelial cultures fluid absorption was inhibited by amiloride. Adenosine 3',5'-monophosphate stimulated fluid secretion in normal epithelial cultures but not in cultures from individuals with CF. In contrast, fluid secretion induced by nucleotide triphosphates (uridine triphosphate or adenosine triphosphate) was unaltered in cultures of epithelia from patients with CF, suggesting an approach to the treatment of CF.
Jiang
C
C
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Finkbeiner
W E
WE
Widdicombe
J H
JH
McCray
P B
PB
Miller
S S
SS
D000042:Absorption; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology
D015222:Sodium Channels; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D000242:Cyclic AMP; D014544:Uridine Triphosphate