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

TLDR

Monoclonal antibody MRK16 was employed to map the cellular distribution of the MDR1‑encoded P‑glycoprotein in normal human tissues. P‑glycoprotein is concentrated in a few specific sites, with minimal expression in most tissues but prominent localization on the apical surfaces of epithelial cells in liver bile canaliculi, pancreatic ductules, renal proximal tubules, colonic and jejunal epithelium, and diffusely in adrenal cortex and medulla, suggesting a role in secretion of metabolites and anticancer drugs.

Abstract

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.