Hepatic uptake of protein-bound ligands: effect of an unstirred
disse space.
Schwab, Andreas J., and Carl A. Goresky.
McGill University Medical Clinic in the Montreal General Hospital
and the Departments of Medicine and Physiology, McGill University,
Montreal, Quebec, Canada
APStracts 3:0005G, 1996.
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
[mu]m 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): G872DG884, 1991]. Ligand is carried across the unstirred layer
by albumin, producing a deviation from binding equilibrium both
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 [mu]m albumin and 0.01 [mu]m oleate to 78% at 0.5 [mu]m
albumin and 0.05 [mu]M oleate. Diffusion through the unstirred layer
and across the cell membrane were found, in the model, to contribute
to the overall resistance to oleate uptake in a complementary
fashion.
Received 21 December 1994; accepted in final form 27 November
1995.
APS Manuscript Number G495-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96