Effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on alpha-aminoisobutyrate uptake in friend Erythroleukemic cells.
In Friend erythroleukemic cells, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increases the rate of influx as well as the steady-state accumulation of the amino acid transport probe alpha-aminoisobutyric acid (AIB). This nonmetabolizable analog is concentrated in these cells by utilizing the energy of the Na+ electrochemical gradient. The effect of TPA is to increase the ouabain-sensitive component of uptake of AIB (and of the K+ analog 86Rb+). Transport changes are not observed until 30 min after application of the promoter and reach a maximum in about 6 hr. The effects are blocked by cycloheximide. The flux results are consistent with a model in which the membrane potential is increased and, with it, the driving force on the coupled Na+-AIB movement. The effect is possibly mediated by a change in electrogenicity of the Na:K pump. TPA raises the steady-state accumulation levels of AIB. By altering external K+ in the presence of valinomycin, the membrane potential may be adjusted and, with it, the accumulation of AIB. Over a wide range of membrane potentials, TPA-treated cells accumulate more AIB than do controls, suggesting a possible change in the internal Na+ activity.
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002999:Clone Cells; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D008564:Membrane Potentials; D010704:Phorbols / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000621:Aminoisobutyric Acids; D010704:Phorbols; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium