Biomaterial Database

Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver. 2013

Jeff L Staudinger, and Sarah Woody, and Mengxi Sun, and Wenqi Cui

Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas 66045, USA. stauding@ku.edu

Adverse drug events (ADEs) are a common cause of patient morbidity and mortality and are classically thought to result, in part, from variation in expression and activity of hepatic enzymes of drug metabolism. It is now known that alterations in the expression of genes that encode drug- and bile-acid-transporter proteins in both the gut and liver play a previously unrecognized role in determining patient drug response and eventual clinical outcome. Four nuclear receptor (NR) superfamily members, including pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (NR1I3), farnesoid X receptor (NR1H4), and vitamin D receptor (NR1I1), play pivotal roles in drug- and bile-acid-activated programs of gene expression to coordinately regulate drug- and bile-acid transport activity in the intestine and liver. This review focuses on the NR-mediated gene activation of drug and bile-acid transporters in these tissues as well as the possible underlying molecular mechanisms.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008658	Inactivation, Metabolic	Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.	Detoxication, Drug, Metabolic,Drug Detoxication, Metabolic,Metabolic Detoxication, Drug,Detoxification, Drug, Metabolic,Metabolic Detoxification, Drug,Metabolic Drug Inactivation,Detoxication, Drug Metabolic,Detoxication, Metabolic Drug,Detoxification, Drug Metabolic,Drug Inactivation, Metabolic,Drug Metabolic Detoxication,Drug Metabolic Detoxification,Inactivation, Metabolic Drug,Metabolic Drug Detoxication,Metabolic Inactivation
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090702	Constitutive Androstane Receptor	A member of the nuclear receptor superfamily (subfamily 1, group I, member 3 [NR1i3]) involved, along with PREGNANE X RECEPTOR, in regulation of cellular responses to the exogenous and endogenous chemicals such as detoxification of XENOBIOTICS.	CAR Nuclear Receptor,CAR Orphan Nuclear Receptor,Constitutive Active Receptor,Constitutive Androstane Receptor beta,Active Receptor, Constitutive,Androstane Receptor, Constitutive,Nuclear Receptor, CAR,Receptor, CAR Nuclear,Receptor, Constitutive Active
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001647	Bile Acids and Salts	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.	Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D041981	Gastrointestinal Tract	Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).	Digestive Tract,GI Tract,Digestive Tracts,GI Tracts,Gastrointestinal Tracts