Corvera S, Schwarz K R, Graham R M, García-Sáinz J A
J Biol Chem. 1986 Jan 15;261(2):520-6.
4 beta-Phorbol 12-myristate 13-acetate (PMA) modified the metabolic actions of three calcium-dependent hormones in different ways. The stimulations of glycogenolysis ureogenesis and phosphatidylinositol labeling produced by alpha 1-adrenergic agonist was blocked by the phorbol ester. In contrast, PMA slightly increased the stimulation of ureogenesis produced by low concentration of angiotensin II without modifying the maximal response. No effect of PMA was observed on the stimulation of ureogenesis induced by vasopressin. The stimulation of phosphatidylinositol labeling induced by vasopressin was decreased by PMA, whereas that induced by angiotensin II was not affected. In intact freshly isolated hepatocytes, [3H]prazosin binds with high affinity to a site which displays the characteristics of alpha 1-adrenergic receptor. Competitive inhibition studies with (-)-epinephrine reveal two different sites for this agonist: a high affinity site (Kd 9 nM) and a low affinity site (Kd 2 microM). In the presence of phorbol esters, (-)-epinephrine binding data now show the presence of a single class of low affinity sites, with similar affinity to those present in control cells. Thus, the inhibition of hepatocyte alpha 1-adrenergic action by PMA may be related to the loss of high affinity binding sites caused by the tumor promoter.
4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）以不同方式改变了三种钙依赖性激素的代谢作用。α1-肾上腺素能激动剂所产生的糖原分解、尿素生成及磷脂酰肌醇标记的刺激作用被佛波醇酯阻断。相反，PMA略微增强了低浓度血管紧张素II所产生的尿素生成刺激作用，而未改变最大反应。未观察到PMA对血管加压素诱导的尿素生成刺激作用有影响。PMA使血管加压素诱导的磷脂酰肌醇标记刺激作用减弱，而血管紧张素II诱导的该刺激作用则未受影响。在完整的新鲜分离肝细胞中，[3H]哌唑嗪以高亲和力与一个表现出α1-肾上腺素能受体特征的位点结合。用（-）-肾上腺素进行的竞争性抑制研究揭示了该激动剂的两个不同位点：一个高亲和力位点（Kd 9 nM）和一个低亲和力位点（Kd 2 μM）。在佛波醇酯存在的情况下，（-）-肾上腺素结合数据现在显示存在一类单一的低亲和力位点，其亲和力与对照细胞中的相似。因此，PMA对肝细胞α1-肾上腺素能作用的抑制可能与肿瘤促进剂导致的高亲和力结合位点丧失有关。
