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

1. Previous studies demonstrate that volume-sensitive chloride current s are distinctly activated in cervical cancer cells, but not in human papillomavirus (HPV)-immortalized and normal cervical cells. In the pr esent 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 effe ctively blocked by various Cl- channel blockers with a similar potency in blocking volume-sensitive Cl- channels: forskolin>5-nitro-2-(3-phe nyl-propylamino)-benzoic acid acetamido-4'-isothiocyanastilbene-2,2'-d isulphonic acid ITS)>4,4'-diisothiocyanatostilbene-2,2-disulphonic aci d (DIDS)>furosemide. The taurine influx was also abolished by pertussi s toxin. In contrast, Na+-independent volume-activated taurine transpo rt was not significantly activated in HPV-immortalized Z183A cells and in normal cervical cells. 3. Exposure of HT-3 cells to hypotonic medi um also resulted in a marked increase in taurine efflux. The volume-ac tivated taurine efflux was osmolarity dependent and the pattern of pha rmacological inhibition by Cl- channel blockers was indistinguishable from that for taurine uptake. 4. These results suggest that volume-sen sitive Cl- channels in HT-3 cells can mediate the transport of amino a cids. In addition, the pertussis toxin-sensitive G-protein is linked w ith the activation of this transport mechanism.