Characterizing mechanisms of hepatic bile acid transport utilizing isolated membrane vesicles.
Utilizing the above-outlined approaches, mechanisms of hepatic bile acid transport have been characterized in membrane vesicles of rat liver, particularly for the conjugated trihydroxy bile acid, taurocholic acid. Uptake across the sinusoidal membrane is carrier mediated and coupled to the transmembrane sodium gradient. This carrier has an apparent Km between 30 to 50 microM and a Vmax between 4 to 6 nmol mg-1 protein min-1. Furthermore, Na+ gradient-dependent sinusoidal uptake of taurocholate can be stimulated by low concentrations of albumin. There is controversy as to whether the process is electrogenic. Although photoaffinity labeling studies indicate that an additional carrier for Na(+)-dependent bile acid uptake is also present at the sinusoidal membrane, this carrier has so far not been characterized in membrane vesicles. The proposition that pH gradient-driven furosemide-sensitive cholic acid uptake into sinusoidal membrane vesicles may represent carrier-mediated hydroxyl/cholate exchange must be revised on the basis of the recent findings that (1) true initial uptake rates are not saturable; (2) pH gradient-driven cholate uptake is also found in liposomes; and (3) furosemide also inhibits pH gradient-driven cholate uptake in liposomes. The mechanisms of transcellular transport of bile acids have been studied less extensively, but Na(+)-independent carrier-mediated taurocholic acid transport has been demonstrated in purified subcellular fractions such as rat liver microsomes and Golgi membranes. Finally, transport studies in canalicular rat liver plasma membrane vesicles indicate that canalicular excretion of bile acids is also a carrier-mediated process that may be driven, at least in part, by the physiologic electrical potential gradient, and that preferentially transports trihydroxy and conjugated dihydroxy bile acids.
Boyer
J L
JL
Meier
P J
PJ
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002458:Cell Fractionation / Q000379:methods; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004848:Epithelium / Q000378:metabolism; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D012996:Solutions; D013696:Temperature
D001647:Bile Acids and Salts; D007202:Indicators and Reagents; D012996:Solutions; D008274:Magnesium; D002118:Calcium