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

Yamaguchi, Hiroaki; Sugie, Misa; Okada, Masahiro; Mikkaichi, Tsuyoshi; Toyohara, Takafumi; Abe, Takaaki; Goto, Junichi; Hishinuma, Takanori; Shimada, Miki; Mano, Nariyasu

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

Yamaguchi, Hiroaki; Sugie, Misa; Okada, Masahiro et al.

Drug metabolism and pharmacokinetics, 2010, 25(3), 314-317

Permalink : https://hdl.handle.net/2115/50982

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アクセス権	open access
URI	https://hdl.handle.net/2115/50982
タイトル	Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1.
著者	Yamaguchi, Hiroaki ; Sugie, Misa ; Okada, Masahiro ; Mikkaichi, Tsuyoshi ; Toyohara, Takafumi ; Abe, Takaaki ; Goto, Junichi ; Hishinuma, Takanori ; Shimada, Miki ; Mano, Nariyasu
e-Rad_Researcher 80400373 著者名 Yamaguchi, Hiroaki
著者名 Sugie, Misa
著者名 Okada, Masahiro
著者名 Mikkaichi, Tsuyoshi
著者名 Toyohara, Takafumi
e-Rad_Researcher 80292209 著者名 Abe, Takaaki
e-Rad_Researcher 80006337 著者名 Goto, Junichi
e-Rad_Researcher 20199003 著者名 Hishinuma, Takanori
著者名 Shimada, Miki
e-Rad_Researcher 50323035 著者名 Mano, Nariyasu
言語	英語
キーワード	OATP4C1
	estrone 3-sulfate
	digoxin
	mutual inhibition
	recognition site
発行日	2010
出版者	Japanese Society for the Study of Xenobiotics
収録物名	Drug metabolism and pharmacokinetics
巻(号)	25(3)
ページ	314-317
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	1880-0920
関連情報	PMID 20610891
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.2133/dmpk.25.314