Canalicular transport: discovery of ATP-dependent mechanisms. 1993

M Vore
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536.

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.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001648 Bile Canaliculi Minute intercellular channels that occur between liver cells and carry bile towards interlobar bile ducts. Also called bile capillaries. Bile Canaliculus,Canaliculi, Bile,Canaliculus, Bile
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D013656 Taurocholic Acid The product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic. Cholyltaurine,Taurine Cholate,Taurocholate,Sodium Taurocholate,Taurocholate Sodium,Taurocholic Acid, (5 alpha)-Isomer,Taurocholic Acid, (7 beta)-Isomer,Taurocholic Acid, Monolithium Salt,Taurocholic Acid, Monosodium Salt,Taurocholate, Sodium

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