Saturation of hepatic transport of taurocholate in rats in vivo
Autor: | X. Deroubaix, Ernest Feytmans, Eric Depiereux, Thierry Coche |
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Rok vydání: | 1991 |
Předmět: |
Taurocholic Acid
medicine.medical_specialty Physiology Models Biological Taurochenodeoxycholic Acid Excretion Reaction rate constant In vivo Physiology (medical) Internal medicine medicine Animals Bile Infusions Intravenous Hepatology Chemistry Gastroenterology Hepatic transport Biological Transport Rats Inbred Strains Intravenous Infusions Rats Kinetics Endocrinology Liver Female Saturation (chemistry) |
Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 260:G189-G196 |
ISSN: | 1522-1547 0193-1857 |
DOI: | 10.1152/ajpgi.1991.260.2.g189 |
Popis: | 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. |
Databáze: | OpenAIRE |
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