Thiebaut F, Tsuruo T, Hamada H, Gottesman M M, Pastan I, Willingham M C
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735-8. doi: 10.1073/pnas.84.21.7735.
Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated in a small number of specific sites. Most tissues examined revealed very little P-glycoprotein. However, certain cell types in liver, pancreas, kidney, colon, and jejunum showed specific localization of P-glycoprotein. In liver, P-glycoprotein was found exclusively on the biliary canalicular front of hepatocytes and on the apical surface of epithelial cells in small biliary ductules. In pancreas, P-glycoprotein was found on the apical surface of the epithelial cells of small ductules but not larger pancreatic ducts. In kidney, P-glycoprotein was found concentrated on the apical surface of epithelial cells of the proximal tubules. Colon and jejunum both showed high levels of P-glycoprotein on the apical surfaces of superficial columnar epithelial cells. Adrenal gland showed high levels of P-glycoprotein diffusely distributed on the surface of cells in both the cortex and medulla. These results suggest that the protein has a role in the normal secretion of metabolites and certain anti-cancer drugs into bile, urine, and directly into the lumen of the gastrointestinal tract.
单克隆抗体MRK16用于确定多药耐药基因（MDR1）产物P-糖蛋白在正常人体组织中的位置。发现该蛋白集中在少数特定部位。大多数检测的组织显示P-糖蛋白含量极少。然而，肝脏、胰腺、肾脏、结肠和空肠中的某些细胞类型显示出P-糖蛋白的特异性定位。在肝脏中，P-糖蛋白仅在肝细胞的胆小管前沿和小胆管上皮细胞的顶端表面被发现。在胰腺中，P-糖蛋白在小导管上皮细胞的顶端表面被发现，但在较大的胰管中未发现。在肾脏中，P-糖蛋白集中在近端小管上皮细胞的顶端表面。结肠和空肠在浅表柱状上皮细胞的顶端表面均显示出高水平的P-糖蛋白。肾上腺显示P-糖蛋白在皮质和髓质细胞表面均有高水平的弥散分布。这些结果表明，该蛋白在代谢产物和某些抗癌药物正常分泌到胆汁、尿液以及直接进入胃肠道管腔中发挥作用。
