Hepatic uptake of protein-bound ligands: effect of an unstirred Disse space

Abstract

Uptake of protein-bound substances by the liver was modeled considering concurrent depletion of unbound ligand (i.e., not bound to protein)along the length of a sinusoid as well as within a 0.5-micron unstirred boundary layer at the surface of the hepatic parenchymal cells. The development completes a previous exploration of Weisiger et al. [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G872-G884, 1991]. Ligand is carried across the unstirred layer by albumin, producing a deviation from binding equilibrium inside and outside the unstirred layer. The resulting differential equations have a closed solution. In the case of tight binding, the unbound ligand in the sinusoid is in a quasi-steady state, and the unbound fraction becomes constant along the flow path, except for a very short section at its beginning. During hepatic oleate uptake, the unbound oleate concentration rises from 39% of the equilibrium value at 0.1 microM albumin and 0.01 microM oleate to 78% at 0.5 microM albumin and 0.05 microM oleate. diffusion through the unstirred layer and across the cell membrane was found, in the model, to contribute to the overall resistance to oleate uptake in a complementary fashion.