AbstractThe level of occupancy of a single class of high‐affinity (3H)‐phorbol 12, 13‐dibutyrate (PDBu) bindings sites (Kd = 26 nM) in quiescent Swiss 3T3 cells was correlated with the dose of PDBu required to stimulate rapid (increase in86Rb uptake, decrease in epidermal growth factor receptor affinity) and long‐term (induction of 2‐deoxyglucose uptake, initiation of DNA synthesis) events of the proliferative response. Further, structural analogues of PDBu showed identical relative potencies in the inhibition of (3H)‐PDBu binding and stimulation of DNA synthesis. Finally, prolonged (24‐hour) incubation of Swiss 3T3 or whole mouse embryo fibroblasts with 400 nM PDBu led to a decrease in the number of (3H)‐PDBu binding sites (down‐regulation) with a parallel loss of rapid and long‐term responses of the cells to PDBu (desensitization). These findings indicate that the high‐affinity (3H)‐PDBu binding sites mediate the mitogenic effects of phorbol ester
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