Effect of the Tumor Promoter 12- O-Tetradecanoylphorbol-13-acetate on a-Aminoisobutyrate Uptake in Friend Erythroleukemic Cells1

In Friend erythroleukemic cells, the tumor promoter 12-Otetradecanoylphorbol-13-acetate (TPA) increases the rate of influx as well as the steady-state accumulation of the amino acid transport probe a-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 mem brane 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.