Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 24248-24252 |
| Number of pages | 5 |
| Journal | Journal of Biological Chemistry |
| Volume | 267 |
| Issue number | 34 |
| Publication status | Published - 1992 Dec 5 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. / Ueda, Kazumitsu; Okamura, Noboru; Hirai, Midori; Tanigawara, Yusuke; Saeki, Tohru; Kioka, Noriyuki; Komano, Tohru; Hori, Ryohei.
In: Journal of Biological Chemistry, Vol. 267, No. 34, 05.12.1992, p. 24248-24252.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone
AU - Ueda, Kazumitsu
AU - Okamura, Noboru
AU - Hirai, Midori
AU - Tanigawara, Yusuke
AU - Saeki, Tohru
AU - Kioka, Noriyuki
AU - Komano, Tohru
AU - Hori, Ryohei
PY - 1992/12/5
Y1 - 1992/12/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026487058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026487058&partnerID=8YFLogxK
M3 - Article
C2 - 1360010
AN - SCOPUS:0026487058
VL - 267
SP - 24248
EP - 24252
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 34
ER -