Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1.
نویسندگان
چکیده
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.
منابع مشابه
Short Communication Transport of Estrone 3-sulfate Mediated by Organic Anion Transporter OATP4C1: Estrone 3-sulfate binds to the Different Recognition Site for Digoxin in OATP4C1
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. Author(s) Yamaguchi, Hiroaki; Sugie, Misa; Okada, Masahiro; Mikkaichi, Tsuyoshi; Toyohara, Takafumi; Abe, Takaaki; Goto, Junichi; Hishinuma, Takanori; Shimada, Miki; Mano, Nariyasu Citation Drug metabolism and pharmacokinetics, 25(...
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عنوان ژورنال:
- Drug metabolism and pharmacokinetics
دوره 25 3 شماره
صفحات -
تاریخ انتشار 2010