Molecular aspects of organic compound transport across the plasma membrane of hepatocytes.
Many organic compounds are taken up from the blood by membrane transporters, taken across the sinosuidal membrane of hepatocytes and then excreted into bile via the bile canalicular membrane. The hepatic uptake of conjugated bile acids is mediated by the sodium taurocholate cotransporting polypeptide. Many organic anions and bulky organic cations are incorporated into hepatocytes by the organic anion transporting polypeptide, while small organic cations are transported by the organic cation transporter. At the canalicular membrane, organic compounds are excreted into bile by ATP-binding cassette transporters which hydrolyse ATP to ADP. Excretion of monovalent bile acids is mediated by the canalicular bile salt transporter and that of organic anions, including divalent bile acid, conjugates, are mediated by the multi-drug resistance-associated protein 2, also termed canalicular multi-specific organic anion transporter. Organic cations are excreted into bile by the multi-drug resistance gene product (MDR) 1 and phospholipids are excreted by MDR3 (mdr2 in mice and rats). The clinical syndromes associated with alterations of these transporters are also discussed.
Kamisako
T
T
Second Department of Internal Medicine, Kinki University School of Medicine, Osakasayama, Japan.
Gabazza
E C
EC
Ishihara
T
T
Adachi
Y
Y
D000818:Animals; D000838:Anions / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001648:Bile Canaliculi / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D009930:Organic Chemicals / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D000838:Anions; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002412:Cations; D009930:Organic Chemicals; D010743:Phospholipids