PXR receptor

The interactions of herbal medicines with P450 3 A4 have already been mentioned and are one of the worst problems with these mixtures . One of the most studied issues is St. John s wort, which induces P450 3A4 as an agonist of the PXR receptor . The induction of P450 3A4 by St. John s wort has been responsible for the loss of the effectiveness of oral contraceptives . The resulting pregnancies... 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

Stanley LA, Horsburgh BC, Ross J et al (2006) PXR and CAR nuclear receptors which play a pivotal role in drug disposition and chemical toxicity. Drug Metab Rev 38 515-597... 

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... 

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... 

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

A different pharmacophore [74], containing only one H-bond acceptor was suggested for the interaction of drugs with the transcriptional regulator PXR (pregnane X receptor) [75]. 

Waxman DJ. P450 gene induction by structurally diverse xenochemicals central role of nuclear receptors CAR, PXR, and PPAR1. Arch Biochem Biophys 1999 369 11-23. 

Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, Mackenzie KI, La-Tour A et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001 98(6) 3 369 3374. 

Orphan Nuclear Receptor PXR-Mediated Gene Regulation in Drug Metabolism and Endobiotic Homeostasis... 

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],... 

Emerging evidence points to the existence of receptor crosstalk between PXR and other nuclear receptors. An early example is the PXR-CAR crosstalk in regulating... 

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