| Title: | Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. |
| Authors: | Yamaguchi, Hiroaki Browse this author →KAKEN DB |
| Okada, Masahiro Browse this author |
| Akitaya, Shou Browse this author |
| Ohara, Hiroshi Browse this author |
| Mikkaichi, Tsuyoshi Browse this author |
| Ishikawa, Haruna Browse this author |
| Sato, Mayumi Browse this author |
| Matsuura, Masaki Browse this author |
| Saga, Toshihide Browse this author |
| Unno, Michiaki Browse this author |
| Abe, Takaaki Browse this author |
| Mano, Nariyasu Browse this author |
| Hishinuma, Takanori Browse this author |
| Goto, Junichi Browse this author |
| Keywords: | nitrobenz-2-oxa-1,3-diazole |
| organic anion-transporting polypeptide 1B1 |
| organic anion-transporting polypeptide 1B3 |
| visualization |
| Issue Date: | Jun-2006 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Journal Title: | Journal of lipid research |
| Volume: | 47 |
| Issue: | 6 |
| Start Page: | 1196 |
| End Page: | 1202 |
| Publisher DOI: | 10.1194/jlr.M500532-JLR200 |
| PMID: | 16534140 |
| Abstract: | 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/50391 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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