Hepatic transport of rose bengal by perfused rabbit liver: the effect of albumin binding on the unidirectional rate constants

Abstract

The effect of albumin on the unidirectional rate constants for the hepatic transport of rose bengal was studied using perfused rabbit livers. Rabbit livers were perfused in a recirculating system with albumin concentrations between 10 and 600 microM and the disappearance of I-125 rose bengal following a bolus injection was recorded. A distributed model of hepatic transport was used to estimate the rate constants for influx into cells, efflux from cells to plasma and biliary excretion. When the rate constants were corrected for albumin binding, the influx, but not the efflux or excretion constant, was a steeply rising function of the perfusate albumin concentration. The result that the influx but not efflux constant is albumin dependent suggests that the phenomenon is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium binding within such a layer. The possibility that the albumin-dependent influx is due to a direct exchange of rose bengal between albumin and a membrane carrier protein is also considered. The independence of the efflux constant and the albumin concentration makes this hypothesis less tenable. However, these data are consistent with the facilitation of albumin-ligand dissociation by liver cells. This analysis represents the first reduction to practice of distributed modeling of disappearance curves. The fact that the excretion constant is independent of the perfusate albumin concentration serves to validate the model that has previously only been considered on theoretical grounds.