AJP - Gastrointestinal and Liver Physiology, Vol 260, Issue 2 189-G196, Copyright © 1991 by American Physiological Society
Saturation of hepatic transport of taurocholate in rats in vivo
X. Deroubaix, T. Coche, E. Depiereux and E. Feytmans
Unite de Biologie Quantitative, Facultes Universitaires Notre-Dame de la Paix, Namur, Belgium.
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.
