The Puzzle of Rates of Cellular Uptake of Protein-Bound Ligands

Abstract

The rates of hepatic and cerebral uptake of physiologically important ligands, such as fatty acids, drugs and dyes, have long been known to be surprisingly high when most ligand is bound to plasma proteins (Baker & Bradley, 1966, Pardridge & Landaw, 1984). The magnitudes of these rates, as well as the unexpected forms of their dependence on protein concentration, have motivated the hypothesis of specific albumin receptors on the hepatocyte (Weisiger, Gollan & Ockner, 1981) helping to translocate the ligand from albumin into the cell; and the hypothesis of a catalytic mechanism of dissociation of ligand from protein at the cellular surface (for example, Baker & Bradley, 1966; Forker & Luxon, 1981). We shall refer to both proposals as facilitation hypotheses. We do not include in this term facilitation of cellular uptake of unbound ligands (see for example Stremmel, Strohmeyer & Berk, 1986).