Inverse relationship between total glutathione S-transferase content and bile acid release in isolated hepatocytes from untreated, phenobarbital pretreated and hypothyroid rats.
The role of cytosolic anion binding proteins (glutathione S-transferases) in the hepatic transport of bile acids remains controversial. To investigate whether increased levels of the hepatocyte total glutathione S-transferase content were associated with changes in the release of bile acids from the hepatocyte, we measured the rate of release of radioactive bile acids in isolated hepatocytes from thyroidectomized, phenobarbital pretreated and untreated rats. The isolated hepatocytes were preincubated with either 14C-cholic acid or 14C-taurocholic acid, and the release rate of radiolabeled bile acids was determined. Hepatocyte total glutathione S-transferase content was measured by rocket immunoelectrophoresis. The release rate of the radiolabeled bile acids was significantly (P less than 0.005) decreased in both hypothyroid and phenobarbital pretreated hepatocytes. The levels of total glutathione S-transferase content were significantly (P less than 0.001) increased in the hepatocytes from both hypothyroid and phenobarbital pretreated animals. Our findings reveal a striking inverse relationship between the total glutathione S-transferase content of the hepatocyte and the release rate of radiolabeled bile acids in isolated hepatocytes from two independent animal models. These observations support the hypothesis that cytosolic anion binding proteins (glutathione S-transferases) may influence the net flux across the hepatocyte plasma membrane largely by limiting efflux.
Wilson
R A
RA
Department of Medicine, University of Washington, Seattle.
Hart
J
J
Hall
T
T
Vincent
S H
SH
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D002855:Chromatography, Thin Layer; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D007037:Hypothyroidism / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism; D013965:Thyroidectomy
D001647:Bile Acids and Salts; D002793:Cholic Acids; D013656:Taurocholic Acid; D005982:Glutathione Transferase; D019826:Cholic Acid; D010634:Phenobarbital