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

Drug Metab Pharmacokinet. 2010;25(3):314-7. doi: 10.2133/dmpk.25.314.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Transport / drug effects*
  • Cell Line
  • Chenodeoxycholic Acid / metabolism
  • Cyclosporine / metabolism
  • Digoxin / metabolism*
  • Dogs
  • Epithelial Cells
  • Estrone / analogs & derivatives*
  • Estrone / metabolism
  • Humans
  • Kidney / cytology
  • Kidney / metabolism
  • Organic Anion Transporters / antagonists & inhibitors
  • Organic Anion Transporters / metabolism*
  • Ouabain / metabolism
  • Pharmacokinetics
  • Sulfobromophthalein / metabolism
  • Triiodothyronine / metabolism


  • Organic Anion Transporters
  • SLCO4C1 protein, human
  • Triiodothyronine
  • Sulfobromophthalein
  • Chenodeoxycholic Acid
  • Estrone
  • Ouabain
  • Digoxin
  • Cyclosporine
  • estrone sulfate