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Abstract

In order to determine if the delayed clearance of organic anions observed in vivo after fasting can be related to an alteration of cell membrane carriers, kinetics of sulfobromophthalein (BSP) uptake were determined in isolated rat liver cells obtained from 48-hr starved rats. Surprisingly, in fasted rats the existence of two carriers can be directly revealed by classical kinetic plots. The high-affinity component, inhibited by Na+-taurocholate, has a Km of 0.5 ± 0.2 μM and a Vmax of 0.2 ± 0.1 nmole per min per 106 cells; the low-affinity component, which is not sensitive to Na+-taurocholate, has a Km of 21.2 ± 3.2 μM and a Vmax of 4.8 ± 0.9 nmoles per min per 106 cells. Comparison with control cells shows that fasting does not modify the total capacity of the liver cell membrane carriers to take up BSP. However, alterations in the kinetic parameters of the two uptake components were observed: a 53% decrease in the affinity of the low-affinity component and a 50% reduction in the capacity of the high-affinity uptake. These alterations, together with the observed decrease in hepatic blood flow and/or the increase in BSP efflux from the hepatocytes, could be involved in the delayed clearance of BSP and other anionic compounds occurring in vivo after fasting.