Document Detail

Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3.
MedLine Citation:
PMID:  16534140     Owner:  NLM     Status:  MEDLINE    
This study sought to clarify the contributions of organic anion-transporting polypeptide (OATP) 1B1 and 1B3 to the liver uptake of chenodeoxycholic acid (CDCA). We synthesized a fluorescent version of CDCA, chenodeoxychilyl-(Nepsilon-NBD)-lysine (CDCA-NBD), to characterize transporter-mediated uptake. CDCA-NBD is efficiently transported by OATP1B1 and OATP1B3 with high affinities. The Michaelis-Menten constants for CDCA-NBD uptake by OATP1B1 and OATP1B3 were 1.45 +/- 0.39 microM and 0.54 +/- 0.09 microM, respectively. By confocal laser scanning microscopy, CDCA-NBD, which is taken up by OATP1B1 and OATP1B3, was observed to localize to the cytosol. We also examined the transport of newly synthesized fluorescent bile acids. NBD-labeled bile acids, including cholic acid, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, were all transported by OATP1B1 and OATP1B3. CDCA-NBD exhibited the highest rate of transport of the five NBD-labeled bile acids examined in OATP1B1- and OATP1B3-expressing cells. Our results suggest that OATP1B1 and OATP1B3 play important roles in CDCA uptake into the liver. Fluorescent bile acids are useful tools to characterize the uptake properties of membrane transporters.
Hiroaki Yamaguchi; Masahiro Okada; Shou Akitaya; Hiroshi Ohara; Tsuyoshi Mikkaichi; Haruna Ishikawa; Mayumi Sato; Masaki Matsuura; Toshihide Saga; Michiaki Unno; Takaaki Abe; Nariyasu Mano; Takanori Hishinuma; Junichi Goto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-13
Journal Detail:
Title:  Journal of lipid research     Volume:  47     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-23     Completed Date:  2006-07-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1196-202     Citation Subset:  IM    
Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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MeSH Terms
Bile Acids and Salts / chemistry,  metabolism,  pharmacokinetics
Biological Transport
Cell Line, Tumor
Chenodeoxycholic Acid / chemistry,  metabolism*,  pharmacokinetics
Microscopy, Confocal
Molecular Structure
Nitrobenzenes / chemistry,  metabolism,  pharmacokinetics
Organic Anion Transport Protein 1 / antagonists & inhibitors,  genetics,  metabolism*
Organic Anion Transporters, Sodium-Independent / genetics,  metabolism*
Oxazoles / chemistry,  metabolism,  pharmacokinetics
Time Factors
Reg. No./Substance:
0/7-chloro-4-nitrobenz-2-oxa-1,3-diazole; 0/Bile Acids and Salts; 0/Nitrobenzenes; 0/Organic Anion Transport Protein 1; 0/Organic Anion Transporters, Sodium-Independent; 0/Oxazoles; 474-25-9/Chenodeoxycholic Acid

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