Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues.

作者：F Thiébaut, T Tsuruo, Hironobu Hamada, Michael M. Gottesman, I Pastan, Mark C. Willingham · 发表于：Proceedings of the National Academy of Sciences · 年份：1987 · DOI：10.1073/pnas.84.21.7735 · 被引用次数：2800 · 研究领域：Drug Transport and Resistance Mechanisms、Pediatric Hepatobiliary Diseases and Treatments、Biochemical and Molecular Research

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.