Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone

Kazumitsu Ueda, Noboru Okamura, Midori Hirai, Yusuke Tanigawara, Tohru Saeki, Noriyuki Kioka, Tohru Komano, Ryohei Hori

研究成果: Article

599 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)24248-24252
ページ数5
ジャーナルJournal of Biological Chemistry
267
発行部数34
出版物ステータスPublished - 1992 12 5
外部発表Yes

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P-Glycoprotein
Aldosterone
Dexamethasone
Progesterone
Hydrocortisone
LLC-PK1 Cells
Vinblastine
Adrenal Cortex
Adrenal Glands
Labeling
Swine
Epithelium
Complementary DNA
Phenotype
Substrates

ASJC Scopus subject areas

  • Biochemistry

これを引用

Ueda, K., Okamura, N., Hirai, M., Tanigawara, Y., Saeki, T., Kioka, N., ... Hori, R. (1992). Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. Journal of Biological Chemistry, 267(34), 24248-24252.

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.

:: Journal of Biological Chemistry, 巻 267, 番号 34, 05.12.1992, p. 24248-24252.

研究成果: Article

Ueda, K, Okamura, N, Hirai, M, Tanigawara, Y, Saeki, T, Kioka, N, Komano, T & Hori, R 1992, 'Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone', Journal of Biological Chemistry, 巻. 267, 番号 34, pp. 24248-24252.
Ueda, Kazumitsu ; Okamura, Noboru ; Hirai, Midori ; Tanigawara, Yusuke ; Saeki, Tohru ; Kioka, Noriyuki ; Komano, Tohru ; Hori, Ryohei. / Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. :: Journal of Biological Chemistry. 1992 ; 巻 267, 番号 34. pp. 24248-24252.
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AU - Saeki, Tohru

AU - Kioka, Noriyuki

AU - Komano, Tohru

AU - Hori, Ryohei

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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.

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