Carrier-mediated electrogenic transport of estradiol-17 beta-glucuronide in rat liver BMV.
Estradiol-17 beta-glucuronide (E(2)17G) is one of a series of naturally occurring glucuronide conjugates of the steroid D-ring that induce cholestasis in the rat and nonhuman primate. The present studies characterized the transport of [3H]E(2)17G in basolateral membrane vesicles (BMVs) from male rat liver. The uptake of E(2)17G was temperature dependent, occurred into an osmotically sensitive space, and was saturable, with an apparent Michaelis constant and maximal velocity of 13 microM and 29 pmol.mg protein-1.5 s-1, respectively. Uptake was not coupled to the uptake of Na+ nor to Cl-or OH- exchange but was markedly stimulated by an inside-positive membrane potential. Bromosulfophthalein inhibited the uptake of E217G noncompetitively; estriol-16 alpha-glucuronide, but not estradiol-3-glucuronide or estradiol-3-SO4-17 beta-glucuronide, inhibited the uptake of E(2)17G. Thus E(2)17G is transported as an anion by facilitated diffusion by a system that differs from the multispecific Na(+)-taurocholate cotransport system and the bromosulfophthalein transport system.
Vore
M
M
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536.
Hoffman
T
T
D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers; D004594:Electrophysiology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013696:Temperature
D004337:Drug Carriers; D013448:Sulfobromophthalein; C025483:estradiol-17 beta-glucuronide; D004958:Estradiol; D013656:Taurocholic Acid