Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.
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.
Ueda
K
K
Department of Agricultural Chemistry, Faculty of Agriculture, Kyoto University, Japan.
Okamura
N
N
Hirai
M
M
Tanigawara
Y
Y
Saeki
T
T
Kioka
N
N
Komano
T
T
Hori
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism*; D004351:Drug Resistance / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D015151:Immunoblotting; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008854:Microscopy, Electron; D011374:Progesterone / Q000378:metabolism*; D013552:Swine; D014162:Transfection; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D000450:Aldosterone; D011374:Progesterone; D014747:Vinblastine; D003907:Dexamethasone; D006854:Hydrocortisone