Linked Life Data

11391536

Source:http://linkedlifedata.com/resource/pubmed/id/11391536

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-6
pubmed:abstractText
The organic anion transporting polypeptides, Oatp1 (Slc21a1) and Oatp2 (Slc21a5), mediate hepatic uptake of cardiac glycosides. Previously, we demonstrated that chemicals that increase cytochrome P450s differentially affect hepatic uptake of cardiac glycosides. We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2. Male Sprague-Dawley rats were injected with PB, PCN, 3-methylcholanthrene (3-MC), or vehicle for 4 days. Branched-DNA (bDNA) signal amplification and Western blot analyses were used to assess hepatic Oatp1 and Oatp2 mRNA and protein, respectively. The expression of Oatp1 was not increased by any chemical treatment. Increases in Oatp2 expression were observed from livers of rats treated with PB and PCN, in which PCN caused a robust elevation of Oatp2 mRNA and protein. Oatp2 expression was suppressed in response to 3-MC. To determine the temporal effects of PCN treatment on the expression of Oatp2, rats were administered PCN, livers were extracted at various times, and Oatp2 expression was analyzed. Maximal expression of Oatp2 mRNA was observed at 24 hours and remained elevated, whereas the amount of Oatp2 protein increased throughout the 96-hour interval. The finding that Oatp2 expression increases in response to PB and PCN is consistent with our previous findings that PB and PCN enhance hepatic uptake of cardiac glycosides. These results suggest that Oatp2, but not Oatp1, is inducible by PB and PCN, which imparts the increased capacity of the liver to extract cardiac glycosides from the plasma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1469-78
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2.
pubmed:affiliation
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.