We expressed human MDR1 cDNA isolated from the human adrenal gland in porcine LLC-PK1 cells. A highly polarized epithelium formed by LLC-GA5-COL300 cells that expressed human P-glycoprotein specifically on the apical surface showed a multidrug-resistant phenotype and had 8.3-, 3.4-, and 6.5-fold higher net basal to apical transport of 3H-labeled cortisol, aldosterone, and dexamethasone, respectively, compared with host cells. But progesterone was not transported, although it inhibited azidopine photoaffinity labeling of human P-glycoprotein and increased the sensitivity of multidrug-resistant cells to vinblastine. An excess of progesterone inhibited the transepithelial transport of cortisol by P-glycoprotein. These results suggest that cortisol and aldosterone are physiological substrates for P-glycoprotein in the human adrenal cortex and that substances that efficiently bind to P-glycoprotein are not necessarily transported by P-glycoprotein.
|Number of pages||5|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 1992 Dec 5|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology