VOLUME REGULATORY TAURINE RELEASE IN HUMAN TRACHEAL 9HTEO(-) AND MULTIDRUG-RESISTANT 9HTEO(-) DX CELLS/

The intracellular taurine release evoked by hypotonic shock is accompl ished by volume-activated Cl- channels whose activity has been related to the expression of the multidrug resistance protein (MDR-1). We stu died taurine transport in 9HTEo(-) cells and in the derived cell line 9HTEo(-)/Dx expressing MDR-1. [H-3]taurine release from preloaded cell s increased upon reduction of extracellular osmolality. This process w as not inhibited by preincubation with phorbol 12-myristate 13-acetate but was reduced by inhibitors of volume-sensitive Cl- channels such a s 1,9-dideoxiforskolin, La3+, and arachidonate. Verapamil, a substrate of MDR-1, increased the osmotically evoked taurine efflux. Replacemen t of extracellular Cl- with I- or gluconate or of extracellular Na+ wi th Li+ significantly reduced the taurine efflux, whereas substitution of N-methyl-D-glucamine for Na+ increased it. Application of ATP and 2 -chloroadenosine stimulated the efflux in isotonic medium. No differen ces were seen between 9HTEo(-) and 9HTEo(-)/Dx cells with respect to h ypotonically induced taurine efflux and the response to phorbol ester, channel blockers, ion replacement, and purinergic agents. Our results reveal novel properties of the osmotically induced taurine release an d demonstrate its independence from MDR-1 gene expression.