PT  - JOURNAL ARTICLE
AU  - Sugiyama, Daisuke
AU  - Kusuhara, Hiroyuki
AU  - Shitara, Yoshihisa
AU  - Abe, Takaaki
AU  - Sugiyama, Yuichi
TI  - Effect of 17β-Estradiol-<span class="sc">d</span>-17β-Glucuronide on the Rat Organic Anion Transporting Polypeptide 2-Mediated Transport Differs Depending on Substrates
AID  - 10.1124/dmd.30.2.220
DP  - 2002 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 220--223
VI  - 30
IP  - 2
4099  - http://dmd.aspetjournals.org/content/30/2/220.short
4100  - http://dmd.aspetjournals.org/content/30/2/220.full
SO  - Drug Metab Dispos2002 Feb 01; 30
AB  - 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 andN-(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 theKi values of digoxin and TCA for the transport of TCA and digoxin were 0.58 and 160 μM, respectively. TheKm and Vmaxvalues of TCA and digoxin were 190 μM and 140 pmol/min/mg of protein and 1.1 μM and 6.6 pmol/min/mg of protein, respectively. TheKm and Ki 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 theVmax 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. The American Society for Pharmacology and Experimental Therapeutics