TY - JOUR T1 - 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 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 220 LP - 223 DO - 10.1124/dmd.30.2.220 VL - 30 IS - 2 AU - Daisuke Sugiyama AU - Hiroyuki Kusuhara AU - Yoshihisa Shitara AU - Takaaki Abe AU - Yuichi Sugiyama Y1 - 2002/02/01 UR - http://dmd.aspetjournals.org/content/30/2/220.abstract N2 - 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 ER -