Source:http://linkedlifedata.com/resource/pubmed/id/11602523
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2001-10-16
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| pubmed:abstractText |
Identification and characterization of the pregnane X receptor (PXR) as a key regulator of cytochrome P450 3A (CYP3A) gene expression has led to an increased understanding of the molecular basis of many drug-drug interactions. Mice lacking PXR (PXR-KO) were used in the present study to delineate the role of PXR in regulating hepatomegaly and regulating the activity of CYP3A, organic anion transporting polypeptide-2 (Oatp2), and Cyp7a1 (cholesterol 7alpha-hydroxylase) gene products in vivo. Pregnenolone-16alpha-carbonitrile (PCN) produced hepatomegaly in the wild-type mice but not in the PXR-KO mice. PCN increased both the number of proliferating cell nuclear antigen immuno-positive nuclei and apparent cell size in the wild-type mice but not in the PXR-KO mice. To determine the role PXR plays in regulating CYP3A activity, 6beta-hydroxylation of testosterone and the duration of the loss of righting reflex following administration of the muscle-relaxant zoxazolamine were measured. PCN increased the level of testosterone 6beta-hydroxylation and decreased the duration of the loss of righting-reflex time following zoxazolamine administration in wild-type mice, but did not effect either of these parameters in PXR-KO mice. PCN increased the hepatic uptake of [(3)H]digoxin, an Oatp2 substrate, in wild-type mice but not in the PXR-KO mice. Similarly, PCN decreased bile acid excretion in wild-type mice but not in the PXR-KO mice. Taken together, these data demonstrate a pivotal role for PXR in the regulation of drug-induced hepatomegaly and in the metabolism (CYP3A), transport (Oatp2), biosynthesis (Cyp7a1), and excretion of xenobiotics and bile acids in vivo.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP3A,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transporters...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, N-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Pregnenolone Carbonitrile,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Slc22a7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Xenobiotics,
http://linkedlifedata.com/resource/pubmed/chemical/pregnane X receptor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0090-9556
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
29
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1467-72
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11602523-Animals,
pubmed-meshheading:11602523-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:11602523-Bile Acids and Salts,
pubmed-meshheading:11602523-Cytochrome P-450 CYP3A,
pubmed-meshheading:11602523-Cytochrome P-450 Enzyme System,
pubmed-meshheading:11602523-Hepatocytes,
pubmed-meshheading:11602523-Hepatomegaly,
pubmed-meshheading:11602523-Homeostasis,
pubmed-meshheading:11602523-Mice,
pubmed-meshheading:11602523-Mice, Knockout,
pubmed-meshheading:11602523-Microsomes, Liver,
pubmed-meshheading:11602523-Organic Anion Transporters, Sodium-Independent,
pubmed-meshheading:11602523-Oxidoreductases, N-Demethylating,
pubmed-meshheading:11602523-Pregnenolone Carbonitrile,
pubmed-meshheading:11602523-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:11602523-Receptors, Steroid,
pubmed-meshheading:11602523-Xenobiotics
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| pubmed:year |
2001
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| pubmed:articleTitle |
Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor.
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| pubmed:affiliation |
Department of Pharmacology and Toxicology, University of Kansas Medical Center, Breidenthal Building, Kansas City, KS 66160-7417, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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