Saturation of hepatic transport of taurocholate in rats in vivo.
A single intravenous injection of [14C]taurocholate was followed up in blood and bile of rats submitted to steady intravenous infusions of taurocholate (TC) at rates of 0.0, 0.5, 1.0, and 1.5 mumol.min-1.100 g body wt-1 for at least 30 min. The transport rate constants and the amounts of TC in different compartments were estimated by weighted least-squares adjustment of a six-compartment model to the experimental data (3 compartments for TC distribution in blood, 2 compartments for liver, and 1 compartment for sinusoidal blood space). The saturation of the TC excretion rate was reached at 0.8 mumol.min-1.100 g body wt-1. It was characterized by a decrease of both the uptake and excretion rate constants, by an increase of the ratio of the amounts of TC in the two intrahepatic compartments (H'/H), and by an intrahepatic TC concentration of approximately 2 mM. When tauroursodeoxycholate (TUDC) was infused at a rate of 0.5 mumol.min-1.100 g body wt-1 together with TC at a rate of 1.5 mumol.min-1.100 g body wt-1, the TC excretion rate increased to 1.2 mumol.min-1.100 g body wt-1, and the excretion rate constant and H'/H decreased toward control values. These results support the hypothesis that the saturation of the transport of TC is due to TC hepatotoxicity and can be reduced by TUDC. Michaelis-Menten parameters, derived from saturation curves for both uptake and excretion steps, closely matched earlier results, thus confirming the good descriptive capacity of the model.
Deroubaix
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Unité de Biologie Quantitative, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Coche
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T
Depiereux
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Feytmans
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D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D005260:Female; D007262:Infusions, Intravenous; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine