Juliano R L, Ling V
Biochim Biophys Acta. 1976 Nov 11;455(1):152-62. doi: 10.1016/0005-2736(76)90160-7.
Chinese hamster ovary cells selected for resistance to colchicine display pleiotropic cross-resistance to a wide range of amphiphilic drugs. The drug-resistant phenotype is due to a membrane alteration which reduces the rate of drug permeation. Surface labelling studies reveal that drug-resistant Chinese hamster ovary cell membranes possess a carbohydrate-containing component of 170 000 daltons apparent molecular weight which is not observed in wild type cells. Through studies of the metabolic incorporation of carbohydrate and protein precursors, and through the use of selective proteolysis, this component is shown to be a cell surface glycoprotein. Since this glycoprotein appears unique to mutant cells displaying altered drug permeability, we have designated it the P glycoprotein. The relative amount of surface labelled P glycoprotein correlates with the degree of drug resistance in a number of independent mutant and revertant clones. A similar high molecular weight glycoprotein is also present in drug-resistant mutants from another hamster cell line. Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions...
经筛选获得秋水仙碱抗性的中国仓鼠卵巢细胞对多种两亲性药物表现出多效性交叉抗性。这种耐药表型是由于细胞膜改变导致药物渗透速率降低所致。表面标记研究表明，耐药的中国仓鼠卵巢细胞膜具有一种表观分子量为170000道尔顿的含碳水化合物成分，而野生型细胞中未观察到这种成分。通过对碳水化合物和蛋白质前体的代谢掺入研究，以及通过使用选择性蛋白酶解，表明该成分是一种细胞表面糖蛋白。由于这种糖蛋白似乎是显示药物通透性改变的突变细胞所特有的，我们将其命名为P糖蛋白。在许多独立的突变体和回复体克隆中，表面标记的P糖蛋白的相对量与耐药程度相关。另一种仓鼠细胞系的耐药突变体中也存在类似的高分子量糖蛋白。关于多效性耐药分子基础的观察结果，根据一种模型进行了解释，在该模型中，某些表面糖蛋白通过调节疏水膜区域的特性来控制药物渗透……
