[Hepatocellular transport of bile acids and organic anions in infection and SIRS--evidence for different mechanisms for regulating membrane transport proteins].
The alteration of proinflammatory mediators during sepsis and SIRS results in a large variety of adaptive changes of metabolic and physiologic variables. This study investigated the alterations of hepatocellular transport in a rat sepsis model (LPS i.p.) as well as in a model inducing SIRS by sterile abscess formation (turpentine i.m.). Two bile acids (Cholyltaurine and Chemodeoxycholyltaurine) and one organic anion (Sulfolithocholyltaurine) were used as marker substrates to investigate the time course of hepatocellular transport function. Experiments were performed in isolated perfused rat livers and plasma membrane vesicles. During sepsis, both, the transport of bile acids and that of the organic anion was markedly reduced. In contrast no alteration of transport was detected during SIRS. However, biliary secretion of glutathione (+90%) and bile acid independent bile flow (%) were increased. mRNA levels of bile acid and organic anion transport proteins were reduced. The lowest values were noted 12 h after injection of LPS or turpentine. Almost unchanged kinetic parameters during SIRS pointed to a normal population of transporters with regard to quantity and substrate affinity. Therefore it seems that transcriptional regulation plays an important role for the expression of transport proteins during sepsis, whereas posttranscriptional regulation may be of importance during SIRS. The clinical phenomenon of septic cholestasis including jaundice implies endotoxemia and differenciates against SIRS.
D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology*; D008070:Lipopolysaccharides; D027361:Organic Anion Transporters / Q000378:metabolism; D051381:Rats; D012772:Shock, Septic / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*; D013658:Taurolithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*
D017920:Antiporters; D001647:Bile Acids and Salts; D008070:Lipopolysaccharides; D027361:Organic Anion Transporters; C066776:taurolithocholic acid 3-sulfate; D013658:Taurolithocholic Acid