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 lun g carcinoma epithelial (S1) cells was investigated using a macroscopic I-125 efflux assay. Hypotonic challenge of monolayers led to a signif icant (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 chlor ide-containing solution. Neither 100 mM dideoxy-forskolin nor 100 mM v erapamil inhibited the increase in Cl- secretion after hypotonic chall enge, 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 c ells have a volume-regulated Cl- secretory pathway that is independent of the ABC transporter, P-glycoprotein.