Calcium modulates osmosensitive taurine efflux in HeLa cells.
The role of Ca2+ in the signaling transduction pathway involved in osmosensitive taurine efflux in HeLa cells was studied using radiotracer efflux techniques. Taurine efflux induced by extracellular hypotonicity was decreased by 85% by removal of extracellular Ca2+ and simultaneous depletion of intracellular Ca2+ stores with thapsigargin. Extracellular Ca2+ removal, thapsigargin treatment, or addition of Gd3+ all decreased taurine efflux by approximately 50%. To explore the putative signal transduction pathways involved in swelling-induced taurine efflux, HeLa cells were exposed to PP1, an inhibitor of the Src family of tyrosine kinases, the phospholipase C inhibitor U73122, the IP3 receptor antagonist 2-APB, and the generic protein kinase C inhibitor chelerythrine. All of these treatments caused approximately 50% inhibition of taurine release in Ca2+-rich extracellular medium and approximately 85%-90% in Ca2+-free conditions. The inhibitors of the conventional protein kinase C isoforms BIM-1 and Gö6976 reduced taurine efflux to a lesser extent. Acute (10-min) exposure to the phorbol ester tetradecanoyl phorbol acetate (TPA) increased taurine efflux in 25%, whilst overnight exposure had an inhibitory effect decreasing efflux by 22%. A working model for activation of osmosensitive taurine efflux in HeLa cells involving different Ca2+ signaling pathways is presented.
Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago-6530499, Chile.
Pablo
P
Olivero
Andrés
A
Stutzin
D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D009995:Osmosis; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction; D013654:Taurine / Q000378:metabolism
D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D013654:Taurine; D011493:Protein Kinase C; D002118:Calcium