CELLULAR-LOCALIZATION OF THE MULTIDRUG-RESISTANCE GENE-PRODUCT P-GLYCOPROTEIN IN NORMAL HUMAN-TISSUES
CELLULAR-LOCALIZATION OF THE MULTIDRUG-RESISTANCE GENE-PRODUCT P-GLYCOPROTEIN IN NORMAL HUMAN-TISSUES
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DOI：
10.1073/pnas.84.21.7735
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发表时间：
1987-11-01
影响因子：
11.1
通讯作者：
WILLINGHAM, MC
中科院分区：
文献类型：
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作者：
THIEBAUT, F;TSURUO, T;WILLINGHAM, MC
利用单克隆抗体MRK16测定多药耐药基因（MDRI）产物p -糖蛋白在正常人体组织中的位置。这种蛋白质被发现集中在少数特定的位点上。大多数组织检查显示p -糖蛋白非常少。然而，肝脏、胰腺、肾脏、结肠和空肠的某些细胞类型显示p -糖蛋白的特异性定位。在肝脏中，p -糖蛋白仅存在于肝细胞的胆管前部和小胆管上皮细胞的顶端表面。胰腺小管上皮细胞的顶端表面可见p -糖蛋白，而大胰管的顶端表面未见p -糖蛋白。在肾脏中，p -糖蛋白集中于近端小管上皮细胞的顶端表面。结肠和空肠的浅表柱状上皮细胞顶端表面p -糖蛋白含量均较高。肾上腺皮质和髓质细胞表面均可见高水平p -糖蛋白弥漫性分布。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、尿液中，并直接进入胃肠道管腔中发挥作用。
Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDRI), 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.