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| HUMAN P-GLYCOPROTEIN TRANSPORTS CORTISOL, ALDOSTERONE, AND DEXAMETHASONE, BUT NOT PROGESTERONE |
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| Author(s): UEDA K, OKAMURA N, HIRAI M, TANIGAWARA Y, SAEKI T, KIOKA N, KOMANO T, HORI R |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 267 Issue: 34 Pages: 24248-24252 Published: DEC 5 1992 |
| Times Cited: 460 References: 28 |
| 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 H-3-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. |
| Document Type: Article |
| Language: English |
| Reprint Address: UEDA, K (reprint author), KYOTO UNIV, FAC AGR, DEPT AGR CHEM, BIOCHEM LAB, KYOTO 60601, JAPAN |
Addresses:
1. KYOTO UNIV HOSP, FAC MED, DEPT PHARM, KYOTO 60601, JAPAN |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: KA263 |
| ISSN: 0021-9258 |
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