HEPATIC TRANSPORT OF ROSE-BENGAL BY PERFUSED RABBIT LIVER - THE EFFECT OF ALBUMIN-BINDING ON THE UNIDIRECTIONAL RATE CONSTANTS

The effect of albumin on the unidirectional rate constants for the hep atic transport of rose bengal was studied using perfused rabbit livers . Rabbit livers were perfused in a recirculating system with albumin c oncentrations between 10 and 600 mu M and the disappearance of I-125 r ose bengal following a bolus injection was recorded. A distributed mod el of hepatic transport was used to estimate the rate constants for in flux into cells, efflux from cells to plasma and biliary excretion. Wh en the rate constants were corrected for albumin binding, the influx, but not the efflux or excretion constant, was a steeply rising functio n of the perfusate albumin concentration. The result that the influx b ut not efflux constant is albumin dependent suggests that the phenomen on is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium binding within such a layer. The possibility that the a lbumin-dependent influx is due to a direct exchange of rose bengal bet ween albumin and a membrane carrier-protein is also considered. The in dependence 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 a nalysis represents the first reduction to practice of distributed mode ling 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 grou nds.