Constitutive androstane receptors

Chang TKH, Waxman DJ (2006) Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Drug Metab Rev 38 51-73... 

In addition to PXR, the expression of UGT1A1 and several other UGT isoforms have also been reported to be regulated by several other nuclear receptors, including constitutive androstane receptor (CAR) [25,27,28] and peroxisome proliferator activated receptor a (PPARa) [29,30],... 

Xie, W., Yeuh, M.F., Radominska-Pandya, A., Saini, S.P., Negishi, Y., Bottroff, B.S., Cabrera, G.Y., Tukey, R.H. and Evans, R.M. (2003) Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proceedings... 

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. 

Stedman, C.A., Hddle, C., Coulter, S.A., Sonoda, J., Alvarez, J.G., Moore, D.D., Evans, R.M. and Downes, M. (2005) Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proceedings of the National Academy of Sciences of the United States of America, 102, 2063-2068. 

B., Goodwin, B., Liddle, C. Blanchard, S. G., Willson, T.M., Collins, J.L. and Kliewer, S.A (2000) Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. The Journal of Biological Chemistry, 275, 15122-15127. 

Krasowski, M.D., Yasuda, K., Hagey, L.R. and Schuetz, E.G. (2005) Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors). Nuclear Receptor, 3, 1—20. 

Jyrkkarinne, J., Windshugel, B., Makinen, J., Ylisimio, M., Perakyla, M., Poso, A., Sippl, W. and Honkakoski, P. (2005) Amino adds important for ligand specificity of the human constitutive androstane receptor. The Journal of Biological Chemistry, 280, 5960-5971. 

O. Burk, K.A. Arnold, A. Geick, H. Tegude, and M. Eichelbaum. A role for constitutive androstane receptor in the regulation of human intestinal MDR1 expression. Biol Chem. 386 503-513 (2005). 

Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring B, Wrighton SA, Schuetz EG (2003) Hepatic CYP2B6 expression gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression, J Pharmacol Exp Ther 307 906-922... 

D. Moore, S. Shigeaki and D. Wen Xie, The NRIH and NRRII Receptors Constitutive Androstane Receptor, Pregnene X Receptor, Farnesoid... 

Chen Y, Ferguson SS, Negishi M, Goldstein JA. Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter. Mol Pharmacol 2003 64(2) 316-324. 

Figure 5.34 Mechanism of induction of CYP2B6 by a chemical such as the drug phenobarbital. This drug activates a nuclear receptor (CAR).This combines with the retinoid X receptor and binds to PBREM, as specific section of the CYP gene, which stimulates the production of CYP2B6 mRNA leading to the production of CYP2B6 protein and enzyme. Abbreviations CAR, constitutive androstane receptor RXR retinoid X receptor PBREM, phenobarbital-responsive enhancer module.

Increased P450 synthesis requires enhanced transcription and translation. A cytoplasmic receptor (termed AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified, and the translocation of the inducer-receptor complex into the nucleus and subsequent activation of regulatory elements of genes have been documented. A pregnane X receptor (PXR), a member of the steroid-retinoid-thyroid hormone receptor family, has recently been shown to mediate CYP3 A induction by various chemicals (dexamethasone, rifampin) in the liver and intestinal mucosa. A similar receptor, the constitutive androstane receptor (CAR) has been identified for the phenobarbital class of inducers (Sueyoshi, 2001 Willson, 2002). 

Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, Zelcer N, Adachi M, Strom S, Evans RM, Moore DD, Borst P, Schuetz JD. Interactions between hepatic Mrp4 and Sult2A as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 2004 279 22250-22257. 

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