Ichikawa M, Yoshimura A, Sumizawa T, Shudo N, Kuwazuru Y, Furukawa T, Akiyama S
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
J Biol Chem. 1991 Jan 15;266(2):903-8.
P-glycoprotein (P-gp) is thought to mediate the transport of anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype in tumor cells. However, the function of P-gp in normal tissues is still not well understood. We present evidence indicating that the active efflux of several structurally unrelated organic compounds is mediated by P-gp in multidrug-resistant KB (KB-C2) cells and that these compounds interact with P-gp in the kidney and adrenal gland. The photoactive radioactive calcium channel blocker [3H]azidopine labels a protein of approximately 140 kDa in crude membrane fractions from human kidney and adrenal gland and a 130-kDa protein from bovine adrenal gland. These photolabeled proteins are immunoprecipitated with an anti-P-gp antibody. Photolabeling is inhibited by vinblastine, reserpine, and several other organic chemicals. These data indicate that the kidney and adrenal gland express P-gp (or a protein closely related to P-gp) that can interact with several organic compounds and that the P-gp expressed in these tissues has a drug-binding site similar to that of P-gp in KB-C2 cells. Our findings thus strongly support the hypothesis that P-gp can transport a wide variety of organic chemicals as well as anti-cancer drugs and that one of the physiological functions of P-gp is the excretion of certain classes of organic compounds.
P-糖蛋白（P-gp）被认为介导抗癌药物的转运，并与肿瘤细胞的多药耐药（MDR）表型有关。然而，P-gp在正常组织中的功能仍未完全明确。我们提供的证据表明，几种结构不相关的有机化合物在多药耐药的KB（KB-C2）细胞中由P-gp介导主动外排，并且这些化合物在肾脏和肾上腺中与P-gp相互作用。光活性放射性钙通道阻滞剂[3H]叠氮平在人肾和肾上腺的粗膜组分中标记一种约140 kDa的蛋白质，在牛肾上腺中标记一种130 kDa的蛋白质。这些光标记的蛋白质用抗P-gp抗体进行免疫沉淀。光标记受到长春碱、利血平和其他几种有机化学物质的抑制。这些数据表明，肾脏和肾上腺表达P-gp（或与P-gp密切相关的一种蛋白质），它可以与几种有机化合物相互作用，并且在这些组织中表达的P-gp具有与KB-C2细胞中P-gp相似的药物结合位点。因此，我们的发现有力地支持了以下假说：P-gp可以转运多种有机化学物质以及抗癌药物，并且P-gp的生理功能之一是排泄某些种类的有机化合物。
