Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid transport system.
The secretion of bile by the liver is primarily determined by the ability of the hepatocyte to transport bile acids into the bile canaliculus. A carrier-mediated process for the transport of taurocholate, the major bile acid in humans and rats, was previously demonstrated in canalicular membrane vesicles from rat liver. This process is driven by an outside-positive membrane potential that is, however, insufficient to explain the large bile acid concentration gradient between the hepatocyte and bile. In this study, we describe an ATP-dependent transport system for taurocholate in inside-out canalicular membrane vesicles from rat liver. The transport system is saturable, temperature-dependent, osmotically sensitive, specifically requires ATP, and does not function in sinusoidal membrane vesicles and right side-out canalicular membrane vesicles. Transport was inhibited by other bile acids but not by substrates for the previously demonstrated ATP-dependent canalicular transport systems for organic cations or nonbile acid organic anions. Defects in ATP-dependent canalicular transport of bile acids may contribute to reduced bile secretion (cholestasis) in various developmental, inheritable, and acquired disorders.
Nishida
T
T
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Gatmaitan
Z
Z
Che
M
M
Arias
I M
IM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005372:Filipin / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D012265:Ribonucleotides / Q000494:pharmacology; D013656:Taurocholic Acid / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D005372:Filipin; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; D012265:Ribonucleotides; D013656:Taurocholic Acid; D014638:Vanadates; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)