ATP-dependent transport of beta-estradiol 17-(beta-D-glucuronide) in rat canalicular membrane vesicles

Am J Physiol. 1996 Nov;271(5 Pt 1):G791-8. doi: 10.1152/ajpgi.1996.271.5.G791.


The ATP-dependent transport of beta-estradiol 17-(beta-D-glucuronide) (E217G), a cholestatic metabolite of estradiol, was investigated in rat liver canalicular membrane vesicles. ATP-dependent transport was dependent on time and temperature and occurred into an osmotically sensitive space; kinetic analysis indicated a saturable transport system (Michaelis-Menten constant value, 75 microM; maximum transport rate, 598 protein-1). The steroid conjugates estradiol glucuronide, estriol 3-glucuronide, estriol 16 alpha-glucuronide, testosterone glucuronide, and the three-sulfate conjugate of 17G were effective inhibitors of transport. Bromosulfophthalein, S-(2,4-dinitrophenyl)glutathione, and glutathione disulfide, all substrates of the canalicular ATP-dependent non-bile acid organic anion transport system, were also effective inhibitors, whereas taurocholate had no effect on transport. Conversely, E217G inhibited the ATP-dependent transport of S-(2,4-dinitrophenyl)glutathione. Daunorubicin, vinblastine, etoposide, cyclosporin, and PSC-833, substrates/modulators of P-glycoprotein, were also potent inhibitors of E217G transport, and E217G competitively inhibited the ATP-dependent transport of daunorubicin. C219, a monoclonal antibody against P-glycoprotein, inhibited ATP-dependent transport of E217G and daunorubicin but not of taurocholate or S-(2,4-dinitrophenyl)glutathione. These data indicate that E217G is substrate of both the non-bile acid organic anion transport system and P-glycoprotein but not of the ATP-dependent bile acid transport system in canalicular membranes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology
  • Bile Canaliculi / metabolism*
  • Biological Transport / drug effects
  • Cell Membrane / metabolism
  • Estradiol / analogs & derivatives*
  • Estradiol / metabolism
  • Glucuronates / pharmacology
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Kinetics
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology


  • Antineoplastic Agents
  • Glucuronates
  • Ribonucleotides
  • estradiol-17 beta-glucuronide
  • adenosine 5'-O-(3-thiotriphosphate)
  • Estradiol
  • Adenosine Triphosphate
  • Glutathione