Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3.

Yamaguchi, Hiroaki; Okada, Masahiro; Akitaya, Shou et al.

Journal of lipid research, 2006, 47(6), 1196-1202

Permalink : https://hdl.handle.net/2115/50391

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アクセス権
open access
URI
https://hdl.handle.net/2115/50391
タイトル
Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3.
著者
Yamaguchi, Hiroaki ; Okada, Masahiro ; Akitaya, Shou ; Ohara, Hiroshi ; Mikkaichi, Tsuyoshi ; Ishikawa, Haruna ; Sato, Mayumi ; Matsuura, Masaki ; Saga, Toshihide ; Unno, Michiaki ; Abe, Takaaki ; Mano, Nariyasu ; Hishinuma, Takanori ; Goto, Junichi
e-Rad_Researcher
80400373
著者名
Yamaguchi, Hiroaki
著者名
Okada, Masahiro
著者名
Akitaya, Shou
著者名
Ohara, Hiroshi
著者名
Mikkaichi, Tsuyoshi
著者名
Ishikawa, Haruna
著者名
Sato, Mayumi
著者名
Matsuura, Masaki
著者名
Saga, Toshihide
著者名
Unno, Michiaki
著者名
Abe, Takaaki
著者名
Mano, Nariyasu
著者名
Hishinuma, Takanori
著者名
Goto, Junichi
言語
英語
キーワード
nitrobenz-2-oxa-1,3-diazole
organic anion-transporting polypeptide 1B1
organic anion-transporting polypeptide 1B3
visualization
発行日
2006-06
出版者
American Society for Biochemistry and Molecular Biology
収録物名
Journal of lipid research
巻(号)
47(6)
ページ
1196-1202
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
PISSN
0022-2275
EISSN
1539-7262
NCID
AA00701215
関連情報
PMID
16534140
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1194/jlr.M500532-JLR200