| Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat hepatocytes is mediated by Oatp1 and Oatp2. | |
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MedLine Citation:
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PMID: 11981753 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The uptake of the sulfated bile acid sulfolithocholyltaurine (SLCT) was investigated in isolated rat hepatocytes and in HeLa cells transfected with complementary DNAs (cDNAs) of organic anion transporting polypeptides (Oatps) 1 and 2 cloned from rat liver. In hepatocytes, transport of SLCT was greatly reduced by bromosulfophthalein (BSP), estrone sulfate, the precursor bile acids cholyltaurine and lithocholyltaurine, and 4,4'-diisothiocyanostilbene-2-2'-disulfonic acid (DIDS). However, SLCT transport was insensitive to 4-methylumbelliferyl sulfate, harmol sulfate, digoxin, fexofenadine, and lack of sodium ion. Because the estimation of kinetic constants was enhanced with use of inhibitors, BSP (1-50 micromol/L) was added to isolated rat hepatocytes to assess the various transport components for SLCT uptake. The resulting data showed a nonsaturable pathway and at least 2 pathways of different Michaelis-Menten constants (K(m)) (70 and 6 micromol/L) and similar maximum velocities (V(max)) (1.73 and 1.2 nmol/min/mg protein) and inhibition constants of 0.63 and 10.3 micromol/L for BSP. In expression systems, SLCT was taken up by Oatp1 and Oatp2 expressed in HeLa cells with similar K(m) values (12.6 +/- 6.2 and 14.6 +/- 1.9 micromol/L). These K(m) values were comparable to that observed for the high-affinity pathway in rat hepatocytes. In conclusion, the results suggest that transport of SLCT into rat liver is mediated in part by Oatp1 and Oatp2, high-affinity pathways, a lower-affinity pathway of unknown origin, and a nonsaturable pathway that is compatible with a transport system of high K(m) and/or passive diffusion. |
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Authors:
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Ling-Jie Meng; Pijun Wang; Allan W Wolkoff; Richard B Kim; Rommel G Tirona; Alan F Hofmann; K Sandy Pang |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 35 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 2002 May |
Date Detail:
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Created Date: 2002-04-30 Completed Date: 2002-05-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 1031-40 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anions / pharmacology Cholagogues and Choleretics / pharmacokinetics* Choline / pharmacology Gene Expression Hela Cells Hepatocytes / metabolism* Humans Indicators and Reagents / pharmacology Male Organic Anion Transport Polypeptide C / genetics, metabolism Organic Anion Transporters, Sodium-Independent / genetics, metabolism* Rats Rats, Sprague-Dawley Sulfates / pharmacokinetics* Sulfobromophthalein / pharmacology Taurolithocholic Acid / pharmacokinetics* Temperature |
| Grant Support | |
ID/Acronym/Agency:
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DK21506/DK/NIDDK NIH HHS; DK23026/DK/NIDDK NIH HHS; GM54724/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anions; 0/Cholagogues and Choleretics; 0/Indicators and Reagents; 0/Organic Anion Transport Polypeptide C; 0/Organic Anion Transporters, Sodium-Independent; 0/Slc21a1 protein, rat; 0/Sulfates; 297-83-6/Sulfobromophthalein; 516-90-5/Taurolithocholic Acid; 62-49-7/Choline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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