Crandall D L, Herzlinger H E, Saunders B D, Zolotor R C, Feliciano L, Cervoni P
Department of Cardiovascular Research, American Cyanamid Company, Pearl River, NY 10965.
Metabolism. 1993 Apr;42(4):511-5. doi: 10.1016/0026-0495(93)90111-z.
To better understand the role of the mitogenic vasoactive peptide angiotensin II (AII) in growth and differentiation, we have investigated the existence of membrane receptors for this peptide in rat adipocytes. Following isolation of epididymal fat cells, membrane protein was removed and incubated with varying concentrations of 125I-AII with or without submicromolar concentrations of unlabeled AII. Binding of AII was highly specific, rapid, and reversible. Scatchard analysis indicated that adipocyte membranes contain a high-affinity AII receptor with a Kd of 0.90 nmol/L and a binding site concentration (Bmax) of 53.7 fmol/mg protein. Additional pharmacologic analyses resulted in a rank order potency for peptide agonists and antagonists similar to that reported for the vascular receptor. Determination of subtype specificity with selective organic compounds indicated that the epididymal adipocyte receptor was displaced at low concentrations of DuP753, a selective AT1 subtype antagonist. These studies have successfully identified and characterized a high-affinity membrane receptor for AII in fat cells, further establishing adipose tissue as a peripheral site containing regulatory components of the local renin-angiotensin system.
为了更好地理解促有丝分裂血管活性肽血管紧张素II（AII）在生长和分化中的作用，我们研究了大鼠脂肪细胞中该肽膜受体的存在情况。分离附睾脂肪细胞后，去除膜蛋白，并与不同浓度的125I - AII一起孵育，有无亚微摩尔浓度的未标记AII。AII的结合具有高度特异性、快速且可逆。Scatchard分析表明，脂肪细胞膜含有高亲和力的AII受体，解离常数（Kd）为0.90 nmol/L，结合位点浓度（Bmax）为53.7 fmol/mg蛋白。进一步的药理学分析得出肽激动剂和拮抗剂的效价顺序与报道的血管受体相似。用选择性有机化合物测定亚型特异性表明，附睾脂肪细胞受体在低浓度的选择性AT1亚型拮抗剂DuP753作用下被取代。这些研究成功鉴定并表征了脂肪细胞中AII的高亲和力膜受体，进一步确立了脂肪组织作为含有局部肾素 - 血管紧张素系统调节成分的外周部位。
