Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-1-9
pubmed:abstractText
Intestinal absorption and hepatic clearance of drugs, xenobiotics, and bile acids are mediated by transporter proteins expressed at the plasma membranes of intestinal epithelial cells and liver parenchymal cells in a polarized manner. Within enterocytes and hepatocytes, these exogenous or endogenous, potentially toxic compounds may be metabolized by phase I cytochrome P450 (CYP) and phase II conjugating enzymes. Many transporter proteins and metabolizing enzymes are subject to direct translational modification, enabling very rapid changes in their activity. However, to achieve intermediate and longer term changes in transport and enzyme activities, the genes encoding drug and bile acid transporters, as well as the CYP and conjugating enzymes, are regulated by a complex network of transcriptional cascades. These are typically mediated by specific members of the nuclear receptor family of transcription factors, particularly FXR, SHP, PXR, CAR, and HNF-4alpha. Most nuclear receptors are activated by specific ligands, including numerous xenobiotics (PXR, CAR) and bile acids (FXR). The fine-tuning of transcriptional control of drug and bile acid homeostasis depends on regulated interactions of specific nuclear receptors with their target genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0076-6879
pubmed:author
pubmed:issnType
Print
pubmed:volume
400
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
511-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Coordinate transcriptional regulation of transport and metabolism.
pubmed:affiliation
Division of Gastroenterology and Hepatology, University Hospital, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't