Collins M K, Rozengurt E
J Cell Physiol. 1982 Jul;112(1):42-50. doi: 10.1002/jcp.1041120108.
The level of occupancy of a single class of high-affinity (3H)-phorbol 12, 13-dibutyrate (PDBu) binding sites (Kd = 26 nM) in quiescent Swiss 3T3 cells was correlated with the dose of PDBu required to stimulate rapid (increase in 86Rb 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 esters in fibroblastic cells.
在静止的瑞士3T3细胞中，一类高亲和力（3H）佛波醇12,13 - 二丁酸酯（PDBu）结合位点（Kd = 26 nM）的占有率水平与刺激增殖反应的快速（86Rb摄取增加、表皮生长因子受体亲和力降低）和长期（2 - 脱氧葡萄糖摄取诱导、DNA合成启动）事件所需的PDBu剂量相关。此外，PDBu的结构类似物在抑制（3H）-PDBu结合和刺激DNA合成方面表现出相同的相对效力。最后，用400 nM PDBu对瑞士3T3细胞或全小鼠胚胎成纤维细胞进行长时间（24小时）孵育，导致（3H）-PDBu结合位点数量减少（下调），同时细胞对PDBu的快速和长期反应也相应丧失（脱敏）。这些发现表明，高亲和力（3H）-PDBu结合位点介导了佛波醇酯在成纤维细胞中的促有丝分裂作用。
