Hepatic handling of bile salts and protein in the rat during intrahepatic cholestasis.
17 alpha-Ethynyl estradiol-induced cholestasis was used to study the relationship of protein to bile salt transport in liver. The biliary secretion of horseradish peroxidase was unaltered in treated animals despite a 56% reduction in bile flow. Cytochemistry confirmed that estradiol caused no alteration in the handling of tracer. In a second study, the peak biliary secretion of [14C]taurocholate was reduced by approximately 46% in treated animals. The kinetics of 125I-cholyglycylhistamine, a bile salt derivative, were identical to those of taurocholate in control and cholestatic animals. Taurocholate and cholylglycylhistamine secretion were markedly reduced in control animals during competition with unlabeled taurocholate. Quantitative electron microscopic autoradiography with 125I-cholylglycylhistamine revealed a high concentration of grains over the endoplasmic reticulum and the Golgi complex including associated lysosomes and vesicles. These data demonstrate that estradiol markedly inhibits bile salt transport, but not vesicular transport of horseradish peroxidase. Furthermore, estradiol may alter the movement of bile salts through these organelles.
D000818:Animals; D001345:Autoradiography; D001647:Bile Acids and Salts / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000494:pharmacology; D006000:Glycocholic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006632:Histamine / Q000031:analogs & derivatives / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D007457:Iodine Radioisotopes; D011506:Proteins; D004997:Ethinyl Estradiol; D013656:Taurocholic Acid; C023966:cholylglycylhistamine; D006632:Histamine; D006735:Horseradish Peroxidase; D006000:Glycocholic Acid