Downregulation of taurocholate transport by ileal BBM and liver BLM in biliary-diverted rats.
The enterohepatic circulation of bile salts may be substrate dependent. We hypothesize that decreased intestinal delivery of bile salts results in downregulation of ileal and hepatocyte bile salt transport in the biliary-diverted rat. Maximal velocity (Vmax) of taurocholate transport by ileal brush-border membrane (BBM) vesicles was downregulated in the bile-diverted animals by 45.5% (559.9 +/- 57.8 pmol.mg protein-1.min-1 in bile-diverted rats vs. 1,026.6 +/- 170.9 pmol.mg protein-1.min-1 in shams). Similarly, taurocholate transport Vmax by hepatocyte basolateral membrane (BLM) was downregulated by 37.8% (2.62 +/- 0.18 pmol.mg protein-1.min-1 in bile-diverted rats vs. 6.93 +/- 0.41 pmol.mg protein-1.min-1 in shams). Cholesterol content (mumol/mg protein) of the membranes was increased in both BBM (0.478 +/- 0.055 vs. 0.272 +/- 0.029) and BLM (0.410 +/- 0.052 vs. 0.294 +/- 0.044) in diverted rats compared with shams. Fluorescence anisotropy was significantly higher in diverted animals compared with shams for both BBM (0.2333 +/- 0.001 vs. 0.2120 +/- 0.004) and BLM (0.1524 +/- 0.002 vs. 0.1426 +/- 0.005). We conclude that biliary diversion in the rat leads to downregulation of both ileal BBM and hepatocyte BLM taurocholate transport. Alterations in transporter expression caused by diversion may, in part, be mediated by changes in membrane lipid composition or fluidity.
Higgins
J V
JV
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Research Foundation, Cincinnati, Ohio 45299-3039.
Paul
J M
JM
Dumaswala
R
R
Heubi
J E
JE
D000818:Animals; D015904:Biliopancreatic Diversion; D001692:Biological Transport; D015536:Down-Regulation; D007082:Ileum / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000493:pharmacokinetics*
D013656:Taurocholic Acid