| pubmed-article:16760228 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0013227 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0242598 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C1412070 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C1420086 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C1305923 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C1159620 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0597484 | lld:lifeskim |
| pubmed-article:16760228 | lifeskim:mentions | umls-concept:C0087063 | lld:lifeskim |
| pubmed-article:16760228 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:16760228 | pubmed:dateCreated | 2006-8-23 | lld:pubmed |
| pubmed-article:16760228 | pubmed:abstractText | Vectorial transport of bile acids across hepatocytes is a major driving force for bile flow, and bile acid retention in the liver causes hepatotoxicity. The basolateral and apical transporters for bile acids are thought to be targets of drugs that induce cholestasis. Previously, we constructed polarized LLC-PK1 cells that express both a major bile acid uptake transporter human Na+/taurocholate cotransporting polypeptide (SLC10A1) (NTCP) and the bile acid efflux transporter human bile salt export pump (ABCB 11) (BSEP) and showed that monolayers of such cells can be used to characterize vectorial transcellular transport of bile acids. In the present study, we investigated whether cholestasis-inducing drugs could inhibit bile acid transport in such cells. Because fluorescent substrates allow the development of a high-throughput screening method, we examined the transport by NTCP and BSEP of fluorescent bile acids as well as taurocholate. The aminofluorescein-tagged bile acids, chenodeoxycholylglycylamidofluorescein and cholylglycylamidofluorescein, were substrates of both NTCP and BSEP, and their basal-to-apical transport rates across coexpressing cell monolayers were 4.3 to 4.5 times those of the vector control, although smaller than for taurocholate. The well known cholestatic drugs, rifampicin, rifamycin SV, glibenclamide, and cyclosporin A, reduced the basal-to-apical transport and the apical efflux clearance of taurocholate across NTCP- and BSEP-coexpressing cell monolayers. Further analysis indicated that the drugs inhibited both NTCP and BSEP. Our study suggests that such coexpressing cells can provide a useful system for the identification of inhibitors of these two transport systems, including potential drug candidates. | lld:pubmed |
| pubmed-article:16760228 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16760228 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16760228 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16760228 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16760228 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:16760228 | pubmed:issn | 0090-9556 | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:SuzukiHiroshi... | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:SugiyamaYuich... | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:AkitaHidetaka... | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:OnukiReikoR | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:HofmannAlan... | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:MitaSachikoS | lld:pubmed |
| pubmed-article:16760228 | pubmed:author | pubmed-author:HayashiHisami... | lld:pubmed |
| pubmed-article:16760228 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16760228 | pubmed:volume | 34 | lld:pubmed |
| pubmed-article:16760228 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16760228 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16760228 | pubmed:pagination | 1575-81 | lld:pubmed |
| pubmed-article:16760228 | pubmed:dateRevised | 2007-12-3 | lld:pubmed |
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| pubmed-article:16760228 | pubmed:meshHeading | pubmed-meshheading:16760228... | lld:pubmed |
| pubmed-article:16760228 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16760228 | pubmed:articleTitle | Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. | lld:pubmed |
| pubmed-article:16760228 | pubmed:affiliation | Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan. | lld:pubmed |
| pubmed-article:16760228 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16760228 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:16760228 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:16760228 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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