Kiang, and P. D. Berk. J. CZin. Invest. 84:
1325-1333, 1989) that, in a variety of isolated cell types, the
uptake of oleate at physiological albumin concentrations is
consistent with traditional pharmacokinetic theory (i.e., driven
by unbound ligand). Lower albumin concentrations were
associated with a deviant uptake pattern for which alternative
theories have been proposed. Whether other classes of organic
anions exhibit similar behavior is unknown. Therefore, we
examined the effect of albumin on uptake of two widely studied
organic anions, sulfobromophthalein (BSP) and taurocholate.
Initial uptake velocity of [35S]BSP and [3H]taurocholate by
isolated hepatocytes was studied employing a fixed albumin
concentration and ligand-to-albumin molar ratios from 0.01: 1
to 2:1 for taurocholate and 0.03l:l to 0.751 for BSP. In other
experiments, albumin and ligand were altered in parallel,
keeping their molar ratio constant. Unbound taurocholate
concentrations were measured directly by equilibrium dialysis;
unbound BSP concentrations were calculated from published
data (K. J. Baker and S. E. Bradley. J. CZin. Invest. 45:
281-287, 1966). At 600 FM albumin, uptake of both ligands
was a function of the unbound ligand concentration. At low
ligand-to-albumin molar ratios and consequent unbound ligand
concentrations this relationship was linear; over the
entire range of unbound ligand concentrations studied, both
ligands exhibited Michaelis-Menten kinetics, with definable
maximal velocity and Michaelis constant values. At low albumin
concentrations, the relationships between uptake and
unbound ligand were unchanged for taurocholate; however,
BSP exhibited altered kinetics similar to those observed with
oleate. Nontraditional uptake kinetics at low albumin concentrations
appear to correlate with very high affinity for albumin.
organ
