Regulation of taurine transport in Ehrlich ascites tumor cells.
Taurine influx is inhibited and taurine efflux accelerated when the cell membrane of Ehrlich ascites tumor cells is depolarized. Taurine influx is inhibited at acid pH partly due to the concomitant depolarization of the cell membrane partly due to a reduced availability of negatively charged free carrier. These results are in agreement with a 2Na,1C1,1taurine cotransport system which is sensitive to the membrane potential due to a negatively charged empty carrier. Taurine efflux from Ehrlich cells is stimulated by addition of LTD4 and by swelling in hypotonic medium. Cell swelling in hypotonic medium is known to result in stimulation of the leukotriene synthesis and depolarization of the cell membrane. The taurine efflux, activated by cell swelling, is dramatically reduced when the phospholipase A2 is inhibited indirectly by addition of the anti-calmodulin drug pimozide, or directly by addition of RO 31-4639. The inhibition is in both cases lifted by addition of LTD4. The swelling-induced taurine efflux is also inhibited by addition of the 5-lipoxygenase inhibitors ETH 615-139 and NDGA. It is concluded that the swelling-induced activation of the taurine leak pathway involves a release of arachidonic acid from the membrane phospholipids and an increased oxidation of arachidonic acid into leukotrienes via the 5-lipoxygenase pathway. LTD4 seems to act as a second messenger for the swelling induced activation of the taurine leak pathway either directly or indirectly via its activation of the Cl- channels, i.e., via a depolarization of the cell membrane.
Lambert
I H
IH
Institute of Biological Chemistry A, August Krogh Institute, University of Copenhagen, Denmark.
Hoffmann
E K
EK
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D013189:SRS-A / Q000494:pharmacology; D015290:Second Messenger Systems; D013654:Taurine / Q000378:metabolism*
D007038:Hypotonic Solutions; D007473:Ion Channels; D013189:SRS-A; D013654:Taurine