title: Bile acids, nuclear receptors and cytochrome P450.
abstract: This review summarizes the importance of bile acids (BA) as important regulators of various homeostatic mechanisms with detailed focus on cytochrome P450 (CYP) enzymes. In the first part, synthesis, metabolism and circulation of BA is summarized and BA are reviewed as physiological ligands of nuclear receptors which regulate transcription of genes involved in their metabolism, transport and excretion. Notably, PXR, FXR and VDR are the most important nuclear receptors through which BA regulate transcription of CYP genes involved in the metabolism of both BA and xenobiotics. Therapeutic use of BA and their derivatives is also briefly reviewed. The physiological role of BA interaction with nuclear receptors is basically to decrease production of toxic non-polar BA and increase their metabolic turnover towards polar BA and thus decrease their toxicity. By this, the activity of some drug-metabolizing CYPs is also influenced what could have clinically relevant consequences in cholestatic diseases or during the treatment with BA or their derivatives.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. zendulka@med.muni.cz.
authors.forename: J
authors.initials: J
authors.lastname: Juřica
authors.forename: G
authors.initials: G
authors.lastname: Dovrtělová
authors.forename: K
authors.initials: K
authors.lastname: Nosková
authors.forename: O
authors.initials: O
authors.lastname: Zendulka
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System