caa a22 4500 378861913 CHVBK 20180305123348.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375111733 doi (NATIONALLICENCE)gruyter-10.1351/pac200375111733 Biological function and mode of action of nuclear xenobiotic receptors [Elektronische Daten] [J. Sonoda, R. M. Evans] Two related nuclear receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), act as xenobiotic sensors that protect the body from a multitude of foreign chemicals (xenobiotics) and play a central role in the metabolism and clearance of steroids and toxic endogenous lipids (endobiotics). A structurally diverse array of chemicals including pharmaceutical drugs, steroids, herbal extracts, and pesticides activate PXR or CAR. This activation results in induction of overlapping, but yet distinct drug clearance pathways consisting of cytochrome P450 enzymes, conjugating enzymes, drug transporters, and other related proteins. Similar pathways are also utilized to protect the body from toxic compounds of endogenous origin. Thus, the xenobiotic regulatory circuit contributes both to drug-drug and food-drug interactions as well as endocrine disruption. Consistent with the notion that xenobiotic receptors regulate drug clearance, single nucleotide polymorphisms (SNPs) in either the receptors themselves or receptor-binding sites in the regulatory region of genes encoding metabolic enzymes appear to contribute to the polymorphic expression of components of drug clearance pathways. Together, the xenobiotic receptors PXR and CAR confer metabolic immunity via the ability to control an integrated array of target genes. © 2013 Walter de Gruyter GmbH, Berlin/Boston Sonoda J. Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA aut Evans R. M. Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA aut Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 1733-1742 0033-4545 75:11-12<1733 2003 75 pac https://doi.org/10.1351/pac200375111733 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375111733 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sonoda J. Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA aut NATIONALLICENCE 700 1- Evans R. M. Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 1733-1742 0033-4545 75:11-12<1733 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter