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Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.
Open accessAbstract
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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Citations
Cited by
Schinkel, A. H., Mayer, U., Wagenaar, E., Mol, C. A. A. M., van Deemter, L., Smit, J. J. M., van der Valk, M. A., Voordouw, A. C., Spits, H., van Tellingen, O., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4028 · Cited by 937
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance
Marzolini, C. (2004) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2003.09.012 · Cited by 895
P-glycoprotein and multidrug resistance
Gottesman, M. M., Pastan, I., & Ambudkar, S. V. (1996) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(96)80091-8 · Cited by 560
Ishimoto, H., & Jaffe, R. B. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0001 · Cited by 379
Choroid plexus and the blood–cerebrospinal fluid barrier in disease
Solár, P., Zamani, A., Kubíčková, L., Dubový, P., & Joukal, M. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00196-2 · Cited by 365
Metadata
- Authors
- Ueda, K., Okamura, N., Hirai, M., Tanigawara, Y., Saeki, T., Kioka, N., Komano, T., & Hori, R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-12
- Volume
- 267
- Issue
- 34
- Pages
- 24248-24252
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1526872663
- Cited by
- 673
- References
- 0
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- 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. https://doi.org/10.1016/s0021-9258(18)35757-0
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
