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Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1.

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Title: Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1.
Authors: Yamaguchi, Hiroaki Browse this author →KAKEN DB
Sugie, Misa Browse this author
Okada, Masahiro Browse this author
Mikkaichi, Tsuyoshi Browse this author
Toyohara, Takafumi Browse this author
Abe, Takaaki Browse this author →KAKEN DB
Goto, Junichi Browse this author →KAKEN DB
Hishinuma, Takanori Browse this author →KAKEN DB
Shimada, Miki Browse this author
Mano, Nariyasu Browse this author →KAKEN DB
Keywords: OATP4C1
estrone 3-sulfate
digoxin
mutual inhibition
recognition site
Issue Date: 2010
Publisher: Japanese Society for the Study of Xenobiotics
Journal Title: Drug metabolism and pharmacokinetics
Volume: 25
Issue: 3
Start Page: 314
End Page: 317
Publisher DOI: 10.2133/dmpk.25.314
PMID: 20610891
Abstract: Human organic anion transporter OATP4C1 is a member of the OATP family predominantly expressed in the kidney, and contributes to the renal secretion of digoxin. However, little is known about the characteristics of OATP4C1-madiated transport. We examined the transport of estrone 3-sulfate, which is known as a substrate for other OATPs, by OATP4C1-expressing cells. Estrone 3-sulfate was efficiently transported by OATP4C1. The Michaelis-Menten constant for estrone 3-sulfate uptake by OATP4C1 was 26.6+/-4.9 microM. Transport of estrone 3-sulfate was significantly inhibited by triiodothyronine, chenodeoxycholic acid, bromosulfophtalein, and cyclosporine, whereas known substrates of OATP4C1, digoxin and ouabain, did not change OATP4C1-mediated transport. We further examined the mutual inhibition study between estrone 3-sulfate and digoxin. Digoxin partially inhibited the estrone 3-sulfate transport, and estrone 3-sulfate did not significantly inhibit digoxin transport. The estimated IC(50) value of digoxin for OATP4C1-mediated estrone 3-sulfate transport was 119 microM. This value is not comparable with the Michaelis-Menten constant for digoxin uptake by OATP4C1 (7.8 microM) reported by Mikkaichi et al.(1)) In conclusion, we found that estrone 3-sulfate is a novel substrate for OATP4C1. Moreover, our results indicate that estrone 3-sulfate does not bind to the recognition site for digoxin in OATP4C1.
Type: article
URI: http://hdl.handle.net/2115/50982
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山口 浩明

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