Volume-activated taurine transport is differentially activated in human cervical cancer HT-3 cells but not in human papillomavirus-immortalized Z183A and normal cervical epithelial cells.

Abstract

1. Previous studies demonstrate that volume-sensitive chloride currents are distinctly activated in cervical cancer cells, but not in human papillomavirus (HPV)-immortalized and normal cervical cells. In the present study, the Na(+)-independent volume-activated transport of taurine in three cervical cell types was investigated. 2. Osmotic swelling of cervical cancer HT-3 cells suspended in Na(+)-free hypotonic medium led to increased membrane uptake of taurine. This taurine uptake was effectively blocked by various Cl- channel blockers with a similar potency in blocking volume-sensitive Cl- channels: 1,9-dideoxyforskolin > 5-nitro-2-(3-phenyl-propylamino)-benzoic acid (NPPB) > 4-acetamido-4'-isothiocyanastilbene-2,2'-disulphonic acid (SITS) > 4,4'-diisothio-cyanatostilbene-2,2-disulphonic acid (DIDS) > furosemide. The taurine influx was also abolished by pertussis toxin. In contrast, Na(+)-independent volume-activated taurine transport was not significantly activated in HPV-immortalized Z183A cells and in normal cervical cells. 3. Exposure of HT-3 cells to hypotonic medium also resulted in a marked increase in taurine efflux. The volume-activated taurine efflux was osmolarity dependent and the pattern of pharmacological inhibition by Cl- channel blockers was indistinguishable from that for taurine uptake. 4. These results suggest that volume-sensitive Cl- channels in HT-3 cells can mediate the transport of amino acids. In addition, the pertussis toxin-sensitive G-protein is linked with the activation of this transport mechanism.