Extrahepatic obstructive cholestasis reverses the bile salt secretory polarity of rat hepatocytes.
To elucidate the consequences of extrahepatic cholestasis on the structure and function of hepatocytes, we studied the effects of bile duct ligation on the turnover, surface distribution, and functional activity of the canalicular 100-kD bile salt transport protein (cBSTP). Basolateral (blLPM) and canalicular (cLPM) liver plasma membrane vesicles were purified to the same degree from normal and cholestatic rat livers and the membrane bound cBSTP identified and quantitated using polyclonal anti-cBSTP antibodies. Cholestasis of 50 h resulted in an increased release of cBSTP into bile, thereby decreasing its in vivo half-life from 65 to 25 h. Furthermore, a significant portion of cBSTP accumulated at the basolateral surface and in intracellular vesicles of cholestatic hepatocytes. This redistribution of cBSTP was functionally paralleled by decreased and increased electrogenic taurocholate anion transport in cLPM and blLPM vesicles, respectively. These results demonstrate that biliary obstruction causes a reversal of the bile salt secretory polarity of rat hepatocytes. The resulting increase in basolateral (sinusoidal) bile salt efflux might protect hepatocytes from too high an accumulation of toxic bile salts within the cell interior.
Department of Medicine, University Hospital, Zurich, Switzerland.
G
G
Fricker
L
L
Landmann
P J
PJ
Meier
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D001651:Cholestasis, Extrahepatic / Q000378:metabolism* / Q000503:physiopathology; D006913:Hydroxysteroid Dehydrogenases; D008026:Ligation; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology; D013656:Taurocholic Acid / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D013656:Taurocholic Acid; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)