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Effect of Albumin Binding on Extraction of Sulfobromophthalein by Perfused Elasmobranch Liver: Evidence for Dissociation-Limited Uptake

Authors

  • Richard A. Weisiger,

    Corresponding author
    1. Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672; Department of Medicine and Liver Center, University of California, San Francisco, California 94143; and the Liver Study Unit, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
    • Richard A. Weisiger, M.D., Ph.D., Department of Medicine, University of California, San Francisco, California 94143.
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  • Charles M. Zacks,

    1. Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672; Department of Medicine and Liver Center, University of California, San Francisco, California 94143; and the Liver Study Unit, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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  • Neil D. Smith,

    1. Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672; Department of Medicine and Liver Center, University of California, San Francisco, California 94143; and the Liver Study Unit, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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  • James L. Boyer

    1. Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672; Department of Medicine and Liver Center, University of California, San Francisco, California 94143; and the Liver Study Unit, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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Abstract

We investigated the role of serum albumin in the hepatic uptake of organic anions by determining the effect of added bovine albumin on sulfobromophthalein (BSP) uptake in skates, an animal which naturally lacks this protein. A single-pass perfused liver model was used to determine steady-state net uptake rates as the BSP or BSP and albumin concentrations were systematically varied. Results indicated that two different steps in the uptake process are capable of limiting the uptake rate depending on the albumin and BSP concentrations selected. At higher rates of uptake corresponding to higher BSP concentrations (up to 112 μM), saturation kinetics were observed as the BSP concentration was varied, with apparent Kra and Vmax values which were independent of the albumin concentration (0.05 to 0.75%). These data suggest that under these conditions uptake is limited by a saturable step intrinsic to the liver. In contrast, for lower BSP concentrations and albumin concentrations below about 0.5%, a different kinetic pattern was seen which suggested that the rate-limiting step in uptake was transfer of BSP from albumin to the liver. The latter data were found to be consistent with a model in which the limiting step in the transfer process is spontaneous dissociation of the BSP from binding sites on albumin within the sinusoid.

These results suggest that skate liver clears BSP from albumin solutions by a two-step mechanism in which dissociation from albumin is followed by a saturable process consistent with carrier-mediated transport. The albumin concentration and uptake velocity are important factors in determining which of these steps limits the uptake rate. Clearance is efficient and irreversible even though elasmobranch liver lacks high-affinity cytosolic binding proteins for BSP, and elasmobranch plasma does not normally contain albumin.

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