Structure-specific inhibition by bile acids of adenosine triphosphate-dependent taurocholate transport in rat canalicular membrane vesicles.
The adenosine triphosphate (ATP)-dependent transport system is a major determinant of canalicular bile acid secretion. The system transports bile acids and neither organic cations nor non-bile acid organic anions, such as glucuronides or glutathione adducts. To define the structural specificity of the ATP-dependent system, the authors examined the ability of various bile acids to inhibit ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles. Only bile acids with a negative charge inhibited transport, which was unaffected by side chain length. Conjugated, but not unconjugated, mono- and di-hydroxy bile acids inhibited transport. The presence of 7 alpha- and 12 alpha-hydroxylation also influenced inhibition of ATP-dependent taurocholate transport. Inhibition of transport by bile acids was kinetically competitive. These results suggest that the canalicular ATP-dependent bile acid transport system depends on bile acid side chain charge, conjugation, and hydroxylation.
Nishida
T
T
First Department of Surgery, Osaka University Medical School, Japan.
Che
M
M
Gatmaitan
Z
Z
Arias
I M
IM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001648:Bile Canaliculi / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D006900:Hydroxylation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013656:Taurocholic Acid / Q000378:metabolism*
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D000255:Adenosine Triphosphate