Effect of 17β-estradiol-D-β-glucuronide on the rat organic anion transporting polypeptide 2-mediated transport differs depending on substrates

Daisuke Sugiyama, Hiroyuki Kusuhara, Yoshihisa Shitara, Takaaki Abe, Yuichi Sugiyama

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42 Citations (Scopus)


Rat organic anion transporting polypeptide 2 (rOatp2) is a member of the OATP family. It exhibits broad substrate specificity and accepts amphipathic organic anions, cardiac glycosides (digoxin and ouabain; a neutral compound), and organic cations (rocuronium and N-(4,4-azo-n-pentyl)-21-deoxyajamalinium). In the present study, kinetic analyses were carried out to investigate whether taurocholate (TCA), digoxin, and 17β-estradiol-D-17β-glucuronide (E217βG) share the same recognition site on rOatp2 for their transport. The transport of TCA and digoxin was mutually inhibited, and the K1 values of digoxin and TCA for the transport of TCA and digoxin were 0.58 and 160 μM, respectively. The Km and Vmax values of TCA and digoxin were 190μ M and 140 pmol/min/mg of protein and 1.1 μM and 6.6 pmol/min/mg of protein, respectively. The Km and K1 values were consistent. In addition, digoxin (1 μM) and TCA (100 μM) increased the Km values of TCA and digoxin, respectively, but they did not affect the Vmax values, suggesting that their inhibition is competitive. The transport of digoxin via rOatp2 was inhibited slightly by E217βG, whereas the uptake of TCA was stimulated by E217βG in a concentration-dependent manner. These results suggest that rOatp2 has at least two substrate recognition sites, one for TCA and digoxin and the other for E217βG.

Original languageEnglish
Pages (from-to)220-223
Number of pages4
JournalDrug Metabolism and Disposition
Issue number2
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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