Stimulation of 86Rb+ and 32Pi movements in 3T3 cells by prostaglandins and phorbol esters

Abstract

The potent tumor promoter tetradecanoyl phorbol acetate (TPA) induces early changes in ion movements analogous to those induced by prostaglandins E₁ and F_2α. Among the earliest changes induced by TPA is a significant increase in ³²P_i incorporation within 15 minutes incubation of TPA (10⁻⁸−10⁻⁶ M) with post‐confluent Swiss 3T3 mouse embryonic fibroblasts. Similarly, the active phorbol ester homolog 4‐;β‐;OH phorbol didecanoate but not the inactive stereoisomeric 4‐β‐OH phorbol didecanoate stimulated ³²P_i incorporation. Also, TPA at the above concentrations stimulated ⁸⁶Rb⁺ influx shortly after administration. Both fluxes were ouabain‐sensitive in accord with the idea that an early effect of TPA is to alter (Na⁺ + K⁺)−ATPase activity. Further, prostaglandin E₁ (10⁻⁷−10⁻⁶ M) and prostaglandin F_2α (3 × 10⁻⁹−10⁻⁷ M) caused a similar stimulation of ⁸⁶Rb⁺ and ³²P_i uptake. The finding that water‐soluble prostaglandin F_2α also exhibited stimulatory effects indicated that those hormone‐induced responses are not mediated by solvent interactions. The similar responses of phorbol esters and prostaglandin derivatives suggests that phorbol esters and prostaglandin derivatives may act at common membrane sites The finding that stimulatory effects were observed at discrete times in the logarithmic phase of growth suggests that the activation of membrane receptors may be cell‐cycle dependent.