Lack of inhibition by dideoxy-forskolin and verapamil of DIDS-sensitive volume-activated Cl- secretion in human squamous lung carcinoma epithelial cells.
The effect of osmotic stress on Cl- permeability in human squamous lung carcinoma epithelial (S1) cells was investigated using a macroscopic 125I efflux assay. Hypotonic challenge of monolayers led to a significant (P < 0.01) dose-related increase in efflux from pre-loaded cells, returning to pre-activation rates within 10 min. A similar magnitude of response could be produced by challenge with an isotonic low chloride-containing solution. Neither 100 mM dideoxy-forskolin nor 100 mM verapamil inhibited the increase in Cl- secretion after hypotonic challenge, whereas 100 mM DIDS inhibited volume-activated Cl- secretion by 55%. Both Northern and Western blot analysis confirmed the absence of MDR1 mRNA and P-glycoprotein in the S1 cells. We conclude that these cells have a volume-regulated Cl- secretory pathway that is independent of the ABC transporter, P-glycoprotein.
Munkonge
F M
FM
Ion Transport Unit, National Heart and Lung Institute, London, UK.
Osborne
L R
LR
Geddes
D M
DM
Alton
E W
EW
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D048429:Cell Size; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009994:Osmolar Concentration; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002712:Chlorides; D005576:Colforsin; D014700:Verapamil; C047983:1,9-dideoxyforskolin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid