Canalicular transport: discovery of ATP-dependent mechanisms.
Biliary excretion is well recognized as a major pathway for the elimination of xenobiotics which are amphipathic and of high molecular weight. Excretion in bile thus complements the renal elimination of hydrophilic compounds of low molecular weight. The liver metabolizes many endogenous and exogenous compounds, frequently by oxidation reactions followed by conjugation pathways that yield substrates, particularly glucuronide and glutathione conjugates, suitable for secretion into bile. The features of a compound which make it a substrate for biliary secretion, other than that it must be an amphipathic molecule with a high molecular weight, are still not clearly defined. However, the recent discovery of ATP-dependent transport of glucuronide and glutathione conjugates in canalicular membranes has provided the opportunity to understand the mechanism of transport and the substrate specificity and regulation of the transporter(s). It is the purpose of this article to review these discoveries and their implications for toxicology.
Vore
M
M
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D001692:Biological Transport; D004351:Drug Resistance; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005965:Glucuronates; D008562:Membrane Glycoproteins; D015262:Xenobiotics; D013656:Taurocholic Acid; D000255:Adenosine Triphosphate; D005978:Glutathione