Linked Life Data

16686371

Source:http://linkedlifedata.com/resource/pubmed/id/16686371

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-5-11
pubmed:abstractText
Ursodeoxycholate (UDCA) is widely used for the treatment of cholestatic liver disease. After oral administration, UDCA is absorbed, taken up efficiently by hepatocytes, and conjugated mainly with glycine to form glycoursodeoxycholate (GUDC) or partly with taurine to form tauroursodeoxycholate (TUDC), which undergo enterohepatic circulation. In this study, to check whether three basolateral transporters--Na(+)-taurocholate cotransporting polypeptide (NTCP, SLC10A1), organic anion transporting polypeptide (OATP) 1B1 (OATP-C), and OATP1B3 (OATP8)-mediate uptake of UDCA, GUDC, and TUDC by human hepatocytes, we investigated their transport properties using transporter-expressing HEK293 cells and human cryopreserved hepatocytes. TUDC and GUDC could be taken up via human NTCP, OATP1B1, and OATP1B3, whereas UDCA could be transported significantly by NTCP, but not OATP1B1 and OATP1B3 in our expression systems. We observed a time-dependent and saturable uptake of UDCA and its conjugates by human cryopreserved hepatocytes, and more than half of the overall uptake involved a saturable component. Kinetic analyses revealed that the contribution of Na(+)-dependent and -independent pathways to the uptake of UDCA or TUDC was very similar, while the Na(+)-independent uptake of GUDC was predominant. These results suggest that UDCA and its conjugates are taken up by both multiple saturable transport systems and nonsaturable transport in human liver with different contributions. These results provide an explanation for the efficient hepatic clearance of UDCA and its conjugates in patients receiving UDCA therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transport..., http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transporters..., http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transporters..., http://linkedlifedata.com/resource/pubmed/chemical/SLCO1B3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Symporters, http://linkedlifedata.com/resource/pubmed/chemical/Taurochenodeoxycholic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Taurocholic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Ursodeoxycholic Acid, http://linkedlifedata.com/resource/pubmed/chemical/glycoursodeoxycholic acid, http://linkedlifedata.com/resource/pubmed/chemical/sodium-bile acid cotransporter, http://linkedlifedata.com/resource/pubmed/chemical/tauroursodeoxycholic acid
pubmed:status
MEDLINE
pubmed:issn
1543-8384
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
70-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Uptake of ursodeoxycholate and its conjugates by human hepatocytes: role of Na(+)-taurocholate cotransporting polypeptide (NTCP), organic anion transporting polypeptide (OATP) 1B1 (OATP-C), and oatp1B3 (OATP8).
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't