Pregnane-activated receptor

Potassium Competitive Acid Blockers The pregnane X receptor (PXR) is a promiscuous nuclear receptor, that has evolved to protect the body from toxic chemicals. It is activated by a wide variety of xenobiotics including several diugs like rifampicin, hyperforin ( the active ingredient of St. John s wort), clotrimazole and others. PXR heterodimerizes with the... 

The retinoid X receptor (RXR) is a nuclear receptor that binds and is activated by certain endogenous retinoids, such as 9-cis-retinoic acid. RXR is the obligatory heterodimerization partner for a large number of nonclassic steroid nuclear receptors, such as thyroid hoimone receptor, vitamin D3 receptor, peroxisome proliferator-activated receptor and pregnane X receptor. 

Ruhl, R. et al.. Carotenoids and their metabolites are naturally occurring activators of gene expression via the pregnane X receptor. Fur. J. Nutr, 43, 336, 2004. 

Hustert, E., et al., "Natural Protein Variants of Pregnane X Receptor with Altered Transactivation Activity Toward CYP3A4," Drug Metab. Dispos., 29, 1454—1459 (2001). 

Kast, H.R., Goodwin, B., Tarr, P.T., Jones, S.A., Anisfeld, A.M., Stoltz, C.M., Tontonoz, P., Kliewer, S., Willson, T.M. and Edwards, P.A. (2002) Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. Journal of Biological Chemistry, 277, 2908-2915. 

Teng, S., Jekerle, V. and Piquette-Miller, M. (2003) Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metabolism and Disposition, 31,1296-1299. 

Moore, L.B., Goodwin, B., Jones, S.A., Wisely, G.B., Serabjit-Singh, C.J., Willson, T.M., Collins, J.L. and Kliewer, S. A. (2000) St. John s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences of the United States of America, 97, 7500-7502. 

Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid homeostasis. 

Kobayashi, K., Yamagami, S., Higuchi, T., Hosokawa, M. and Chiba, K. (2004) Key structural features of ligands for activation of human pregnane X receptor. Drug Metabolism and Disposition The Biological Fate of Chemicals, 32, 468-472. 

Recently, Geick et al. [79] discovered a complex regulatory cluster of several binding sites for the ligand-activated nuclear receptor, pregnane X receptor... 

Tirona RG, Leake BE, Podust LM, Kim RB. 2004. Identification of amino acids in rat pregnane X receptor that determine species-specific activation. Mol Pharmacol 65(1) 36. 

Tirona, R. G., Leake, B. F., Wolkoff, A. W., and Kim, R. B. (2003) Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J. Pharmacol. Exp. Ther. 304, 223-228. 

Koyano, S., Kurose, K., Saito, Y., et al. (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, 149-154. 

Moore LB, Goodwin B, Jones SA, et al. St. John s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 2000 97 7500-7502. 

Figure 9.10 Illustration depicting DNA elements found in CYP3A genes and the activation of the human pregnane X receptor (PXR) by ligand (RIF) and subsequent transcriptional activation of CYP3A4 gene by the PXR/RXR heterodimer. dNR-1-3, nuclear receptors 1, 2, and 3, respectively PXR, pregnane X receptor RXR, retinoid X receptor RIF, rifampicin SRC-1, steroid receptor co-activator XREM, xenobiotic responsive enhancer module.

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