Prague Med. Rep. 2013, 114, 205-213

https://doi.org/10.14712/23362936.2014.9

Pregnane Xenobiotic Receptors and Their Effect on Drug Elimination from the Organism

Martin Šíma*, I. Netíková, O. Slanař

Institute of Pharmacology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic

References

1. Bain, D. L., Heneghan, A. F., Connaghan-Jones, K. D., Miura, M. T. (2007) Nuclear receptor structure: implications for function. Annu. Rev. Physiol. 69, 201–220. <https://doi.org/10.1146/annurev.physiol.69.031905.160308>
2. Bertilsson, G., Heidrich, J., Svensson, K., Asman, M., Jendeberg, L., Sydow-Bäckman, M., Ohlsson, R., Postlind, H., Blomquist, P., Berkenstam, A. (1998) Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc. Natl. Acad. Sci. USA 95(21), 12208–12213. <https://doi.org/10.1073/pnas.95.21.12208> <PubMed>
3. Blumberg, B., Sabbagh, W., Juguilon, H., Bolado, J., van Meter, C. M., Ong, E. S., Evans, R. M. (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 12(20), 3195–3205. <https://doi.org/10.1101/gad.12.20.3195> <PubMed>
4. Braissant, O., Foufelle, F., Scotto, C., Dauça, M., Wahli, W. (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137(1), 354–366. <https://doi.org/10.1210/endo.137.1.8536636>
5. Chen, Y., Goldstein, J. A. (2009) The transcriptional regulation of the human CYP2C genes. Curr. Drug Metab. 10(6), 567–578. <https://doi.org/10.2174/138920009789375397>
6. Chetty, M., Miller, R., Seymour, M. A. (1998) Phenytoin auto-induction. Ther. Drug Monit. 20(1), 60–62. <https://doi.org/10.1097/00007691-199802000-00011>
7. Cui, X., Thomas, A., Gerlach, V., White, R. E., Morrison, R. A., Cheng, K. C. (2008) Application and interpretation of hPXR screening data: Validation of reporter signal requirements for prediction of clinically relevant CYP3A4 inducers. Biochem. Pharmacol. 76(5), 680–689. <https://doi.org/10.1016/j.bcp.2008.06.016>
8. Desai, P. B., Nallani, S. C., Sane, R. S., Moore, L. B., Goodwin, B. J., Buckley, D. J., Buckley, A. R. (2002) Induction of cytochrome P450 3A4 in primary human hepatocytes and activation of the human pregnane X receptor by tamoxifen and 4-hydroxytamoxifen. Drug Metab. Dispos. 30(5), 608–612. <https://doi.org/10.1124/dmd.30.5.608>
9. Dussault, I., Lin, M., Hollister, K., Wang, E. H., Synold, T. W., Forman, B. M. (2001) Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J. Biol. Chem. 276(36), 33309–33312. <https://doi.org/10.1074/jbc.C100375200>
10. Eichelbaum, M., Burk, O. (2001) CYP3A genetics in drug metabolism. Nat. Med. 7(3), 285–287. <https://doi.org/10.1038/85417>
11. Floyd, M. D., Gervasini, G., Masica, A. L., Mayo, G., George, A. L., Bhat, K., Kim, R. B., Wilkinson, G. R. (2003) Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 13(10), 595–606. <https://doi.org/10.1097/00008571-200310000-00003>
12. Fromm, M. F., Kauffmann, H. M., Fritz, P., Burk, O., Kroemer, H. K., Warzok, R. W., Eichelbaum, M., Siegmund, W., Schrenk, D. (2000) The effect of rifampin treatment on intestinal expression of human MRP transporters. Am. J. Pathol. 157(5), 1575–1580. <https://doi.org/10.1016/S0002-9440(10)64794-3> <PubMed>
13. Germain, P., Staels, B., Dacquet, C., Spedding, M., Laudet, V. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58(4), 685–704. <https://doi.org/10.1124/pr.58.4.2>
14. Giguère, V. (1999) Orphan nuclear receptors: from gene to function. Endocr. Rev. 20(5), 689–725.
15. Glass, C. K. (1994) Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr. Rev. 15(3), 391–407.
16. Goodwin, B., Moore, L. B., Stoltz, C. M., McKee, D. D., Kliewer, S. A. (2001) Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol. Pharmacol. 60(3), 427–431.
17. Harrington, W. R., Sheng, S., Barnett, D. H., Petz, L. N., Katzenellenbogen, J. A., Katzenellenbogen, B. S. (2003) Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression. Mol. Cell. Endocrinol. 206(1–2), 13–22. <https://doi.org/10.1016/S0303-7207(03)00255-7>
18. Huang, Z., Roy, P., Waxman, D. J. (2000) Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Biochem. Pharmacol. 59(8), 961–972. <https://doi.org/10.1016/S0006-2952(99)00410-4>
19. Hustert, E., Zibat, A., Presecan-Siedel, E., Eiselt, R., Mueller, R., Fuss, C., Brehm, I., Brinkmann, U., Eichelbaum, M., Wojnowski, L., Burk, O. (2001) Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab. Dispos. 29(11), 1454–1459.
20. Jacobs, M. N., Dickins, M., Lewis, D. F. (2003) Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (hERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. J. Steroid Biochem. Mol. Biol. 84(2–3), 117–132. <https://doi.org/10.1016/S0960-0760(03)00021-9>
21. Jones, S. A., Moore, L. B., Shenk, J. L., Wisely, G. B., Hamilton, G. A., McKee, D. D., Tomkinson, N. C., LeCluyse, E. L., Lambert, M. H., Willson, T. M., Kliewer, S. A., Moore, J. T. (2000) The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol. 14(1), 27–39. <https://doi.org/10.1210/mend.14.1.0409>
22. Jonker, J. W., Liddle, C., Downes, M. (2012) FXR and PXR: potential therapeutic targets in cholestasis. J. Steroid Biochem. Mol. Biol. 130(3–5), 147–158. <https://doi.org/10.1016/j.jsbmb.2011.06.012> <PubMed>
23. Kawana, K., Ikuta, T., Kobayashi, Y., Gotoh, O., Takeda, K., Kawajiri, K. (2003) Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR. Mol. Pharmacol. 63(3), 524–531. <https://doi.org/10.1124/mol.63.3.524>
24. Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., Perlmann, T., Lehmann, J. M. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92(1), 73–82. <https://doi.org/10.1016/S0092-8674(00)80900-9>
25. Koyano, S., Kurose, K., Saito, Y., Ozawa, S., Hasegawa, R., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Nakajima, T., Matsumoto, K., Akasawa, A., Saito, H., Sawada, J. (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab. Dispos. 32(1), 149–154. <https://doi.org/10.1124/dmd.32.1.149>
26. Krey, G., Braissant, O., L’Horset, F., Kalkhoven, E., Perroud, M., Parker, M. G., Wahli, W. (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol. Endocrinol. 11(6), 779–791. <https://doi.org/10.1210/mend.11.6.0007>
27. Lamba, J. K., Lin, Y. S., Schuetz, E. G., Thummel, K. E. (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv. Drug Deliv. Rev. 54(10), 1271–1294. <https://doi.org/10.1016/S0169-409X(02)00066-2>
28. Lehmann, J. M., McKee, D. D., Watson, M. A., Willson, T. M., Moore, J. T., Kliewer, S. A. (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 102(5), 1016–1023. <https://doi.org/10.1172/JCI3703> <PubMed>
29. Li, T., Chiang, J. Y. (2005) Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription. Am. J. Physiol. Gastrointest. Liver Physiol. 288(1), G74–G84. <https://doi.org/10.1152/ajpgi.00258.2004>
30. Mangelsdorf, D. J., Borgmeyer, U., Heyman, R. A., Zhou, J. Y., Ong, E. S., Oro, A. E., Kakizuka, A., Evans, R. M. (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 6(3), 329–344. <https://doi.org/10.1101/gad.6.3.329>
31. Mu, Y., Stephenson, C. R., Kendall, C., Saini, S. P., Toma, D., Ren, S., Cai, H., Strom, S. C., Day, B. W., Wipf, P., Xie, W. (2005) A pregnane X receptor agonist with unique species-dependent stereoselectivity and its implications in drug development. Mol. Pharmacol. 68(2), 403–413. <https://doi.org/10.1124/mol.105.013292>
32. Orans, J., Teotico, D. G., Redinbo, M. R. (2005) The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges. Mol. Endocrinol. 19(12), 2891–2900. <https://doi.org/10.1210/me.2005-0156>
33. Ozdemir, V., Kalow, W., Tang, B. K., Paterson, A. D., Walker, S. E., Endrenyi, L., Kashuba, A. D. (2000) Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method. Pharmacogenetics 10(5), 373–388. <https://doi.org/10.1097/00008571-200007000-00001>
34. Pascussi, J. M., Drocourt, L., Gerbal-Chaloin, S., Fabre, J. M., Maurel, P., Vilarem, M. J. (2001) Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor. Eur. J. Biochem. 268(24), 6346–6358. <https://doi.org/10.1046/j.0014-2956.2001.02540.x>
35. Scheyer, R. D., Cramer, J. A., Mattson, R. H. (1994) A pharmacodynamic approach to the estimate of carbamazepine autoinduction. J. Pharm. Sci. 83(4), 491–494. <https://doi.org/10.1002/jps.2600830409>
36. Schuetz, E. G. (2004) Lessons from the CYP3A4 promoter. Mol. Pharmacol. 65(2), 279–281. <https://doi.org/10.1124/mol.65.2.279>
37. Sinz, M. W. (2013) Evaluation of pregnane X receptor (PXR)-mediated CYP3A4 drug-drug interactions in drug development. Drug Metab. Rev. 45(1), 3–14. <https://doi.org/10.3109/03602532.2012.743560>
38. Staudinger, J. L., Xu, C., Biswas, A., Mani, S. (2011) Post-translational modification of pregnane x receptor. Pharmacol. Res. 64(1), 4–10. <https://doi.org/10.1016/j.phrs.2011.02.011> <PubMed>
39. Svoboda, M., Riha, J., Wlcek, K., Jaeger, W., Thalhammer, T. (2011) Organic anion transporting polypeptides (OATPs): regulation of expression and function. Curr. Drug Metab. 12(2), 139–153. <https://doi.org/10.2174/138920011795016863>
40. Tian, Y. (2013) Epigenetic regulation of pregnane X receptor activity. Drug Metab. Rev. 45(2), 166–172. <https://doi.org/10.3109/03602532.2012.756012>
41. Wada, T., Gao, J., Xie, W. (2009) PXR and CAR in energy metabolism. Trends Endocrinol. Metab. 20(6), 273–279. <https://doi.org/10.1016/j.tem.2009.03.003>
42. Wang, H., LeCluyse, E. L. (2003) Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clin. Pharmacokinet. 42(15), 1331–1357. <https://doi.org/10.2165/00003088-200342150-00003>
43. Wang, H., Faucette, S. R., Gilbert, D., Jolley, S. L., Sueyoshi, T., Negishi, M., LeCluyse, E. L. (2003) Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. Drug Metab. Dispos. 31(5), 620–630. <https://doi.org/10.1124/dmd.31.5.620>
44. Wang, Y. M., Ong, S. S., Chai, S. C., Chen, T. (2012) Role of CAR and PXR in xenobiotic sensing and metabolism. Expert Opin. Drug Metab. Toxicol. 8(7), 803–817. <https://doi.org/10.1517/17425255.2012.685237> <PubMed>
45. Wentworth, J. M., Agostini, M., Love, J., Schwabe, J. W., Chatterjee, V. K. (2000) St. John’s wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol. 166(3), R11–R16. <https://doi.org/10.1677/joe.0.166R011>
46. Xie, W., Barwick, J. L., Simon, C. M., Pierce, A. M., Safe, S., Blumberg, B., Guzelian, P. S., Evans, R. M. (2000) Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev. 14(23), 3014–3023. <https://doi.org/10.1101/gad.846800> <PubMed>
47. Zhang, B., Xie, W., Krasowski, M. D. (2008) PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics. Pharmacogenomics 9(11), 1695–1709. <https://doi.org/10.2217/14622416.9.11.1695> <PubMed>
48. Zhang, H., LeCulyse, E., Liu, L., Hu, M., Matoney, L., Zhu, W., Yan, B. (1999) Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation. Arch. Biochem. Biophys. 368(1), 14–22. <https://doi.org/10.1006/abbi.1999.1307>
49. Zhang, J., Kuehl, P., Green, E. D., Touchman, J. W., Watkins, P. B., Daly, A., Hall, S. D., Maurel, P., Relling, M., Brimer, C., Yasuda, K., Wrighton, S. A., Hancock, M., Kim, R. B., Strom, S., Thummel, K., Russell, C. G., Hudson, J. R., Schuetz, E. G., Boguski, M. S. (2001) The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 11(7), 555–572. <https://doi.org/10.1097/00008571-200110000-00003>
50. Zhou, C., Tabb, M. M., Sadatrafiei, A., Grün, F., Blumberg, B. (2004) Tocotrienols activate the steroid and xenobiotic receptor, SXR, and selectively regulate expression of its target genes. Drug Metab. Dispos. 32(10), 1075–1082. <https://doi.org/10.1124/dmd.104.000299>
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