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- 1I. Vitamin D receptor-like receptors
1I. Vitamin D receptor-like receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
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Vitamin D (VDR), Pregnane X (PXR) and Constitutive Androstane (CAR) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [1,12]) are members of the NR1I family of nuclear receptors, which form heterodimers with members of the retinoid X receptor family. PXR and CAR are activated by a range of exogenous compounds, with no established endogenous physiological agonists, although high concentrations of bile acids and bile pigments activate PXR and CAR [12].
Receptors
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Vitamin D receptor / NR1I1
C
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Pregnane X receptor / NR1I2
C
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Constitutive androstane receptor / NR1I3
C
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Further reading
* Key recommended reading is highlighted with an asterisk
Banerjee M, Robbins D, Chen T. (2015) Targeting xenobiotic receptors PXR and CAR in human diseases. Drug Discov Today, 20 (5): 618-28. [PMID:25463033]
* Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev, 58 (4): 798-836. [PMID:17132856]
Bikle DD. (2011) Vitamin D: an ancient hormone. Exp Dermatol, 20 (1): 7-13. [PMID:21197695]
Bikle DD. (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol, 21 (3): 319-29. [PMID:24529992]
Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. (2008) Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev, 29 (6): 726-76. [PMID:18694980]
Campbell FC, Xu H, El-Tanani M, Crowe P, Bingham V. (2010) The yin and yang of vitamin D receptor (VDR) signaling in neoplastic progression: operational networks and tissue-specific growth control. Biochem Pharmacol, 79 (1): 1-9. [PMID:19737544]
Chen Y, Tang Y, Guo C, Wang J, Boral D, Nie D. (2012) Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters. Biochem Pharmacol, 83 (8): 1112-26. [PMID:22326308]
Cheng J, Shah YM, Gonzalez FJ. (2012) Pregnane X receptor as a target for treatment of inflammatory bowel disorders. Trends Pharmacol Sci, 33 (6): 323-30. [PMID:22609277]
Danescu LG, Levy S, Levy J. (2009) Vitamin D and diabetes mellitus. Endocrine, 35 (1): 11-7. [PMID:18979202]
Deeb KK, Trump DL, Johnson CS. (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer, 7 (9): 684-700. [PMID:17721433]
Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. (2014) The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer, 14 (5): 342-57. [PMID:24705652]
Gerbal-Chaloin S, Iankova I, Maurel P, Daujat-Chavanieu M. (2013) Nuclear receptors in the cross-talk of drug metabolism and inflammation. Drug Metab Rev, 45 (1): 122-44. [PMID:23330545]
Gonzalez-Sanchez E, Firrincieli D, Housset C, Chignard N. (2015) Nuclear receptors in acute and chronic cholestasis. Dig Dis, 33 (3): 357-66. [PMID:26045270]
Ihunnah CA, Jiang M, Xie W. (2011) Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim Biophys Acta, 1812 (8): 956-63. [PMID:21295138]
Kachaylo EM, Pustylnyak VO, Lyakhovich VV, Gulyaeva LF. (2011) Constitutive androstane receptor (CAR) is a xenosensor and target for therapy. Biochemistry Mosc, 76 (10): 1087-97. [PMID:22098234]
Köhle C, Bock KW. (2009) Coordinate regulation of human drug-metabolizing enzymes, and conjugate transporters by the Ah receptor, pregnane X receptor and constitutive androstane receptor. Biochem Pharmacol, 77 (4): 689-99. [PMID:18606396]
* Long MD, Sucheston-Campbell LE, Campbell MJ. (2015) Vitamin D receptor and RXR in the post-genomic era. J Cell Physiol, 230 (4): 758-66. [PMID:25335912]
Lucock M, Jones P, Martin C, Beckett E, Yates Z, Furst J, Veysey M. (2015) Vitamin D: Beyond Metabolism. J Evid Based Complementary Altern Med, 20 (4): 310-22. [PMID:25878189]
Mani S, Dou W, Redinbo MR. (2013) PXR antagonists and implication in drug metabolism. Drug Metab Rev, 45 (1): 60-72. [PMID:23330542]
Mo L, He J. (2014) Nuclear hormone receptors PXR and CAR and metabolic diseases. Horm Mol Biol Clin Investig, 19 (2): 129-40. [PMID:25390021]
* Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR, Xiao R, Kliewer SA. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol Rev, 58 (4): 742-59. [PMID:17132852]
Oladimeji PO, Chen T. (2018) PXR: More Than Just a Master Xenobiotic Receptor. Mol Pharmacol, 93 (2): 119-127. [PMID:29113993]
Pavek P. (2016) Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions. Front Pharmacol, 7: 456. [PMID:27932985]
Pike JW. (2011) Genome-scale techniques highlight the epigenome and redefine fundamental principles of gene regulation. J Bone Miner Res, 26 (6): 1155-62. [PMID:21611959]
Pittas AG, Dawson-Hughes B. (2010) Vitamin D and diabetes. J Steroid Biochem Mol Biol, 121 (1-2): 425-9. [PMID:20304061]
Plum LA, DeLuca HF. (2010) Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov, 9 (12): 941-55. [PMID:21119732]
Schmuth M, Moosbrugger-Martinz V, Blunder S, Dubrac S. (2014) Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation. Biochim Biophys Acta, 1841 (3): 463-73. [PMID:24315978]
Staudinger JL, Woody S, Sun M, Cui W. (2013) Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver. Drug Metab Rev, 45 (1): 48-59. [PMID:23330541]
Suda T, Masuyama R, Bouillon R, Carmeliet G. (2015) Physiological functions of vitamin D: what we have learned from global and conditional VDR knockout mouse studies. Curr Opin Pharmacol, 22: 87-99. [PMID:25938686]
Timsit YE, Negishi M. (2007) CAR and PXR: the xenobiotic-sensing receptors. Steroids, 72 (3): 231-46. [PMID:17284330]
Urquhart BL, Tirona RG, Kim RB. (2007) Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol, 47 (5): 566-78. [PMID:17442683]
Wang J, Dai S, Guo Y, Xie W, Zhai Y. (2014) Biology of PXR: role in drug-hormone interactions. EXCLI J, 13: 728-39. [PMID:26417296]
Yan J, Xie W. (2016) A brief history of the discovery of PXR and CAR as xenobiotic receptors. Acta Pharm Sin B, 6 (5): 450-452. [PMID:27709013]
References
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NC-IUPHAR subcommittee and family contributors
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Sylvia Christakos |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Cidlowski JA, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Nuclear hormone receptors. Br J Pharmacol. 180 Suppl 2:S223-240.
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