Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding

Y. R. Stollman, U. Gartner, L. Theilmann, N. Ohmi, Allan W. Wolkoff

Research output: Contribution to journalArticle

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Abstract

Bilirubin uptake by the liver is a rapid process of high specificity that has kinetic characteristics which suggest carrier-mediation. In the circulation, bilirubin is readily bound to albumin, from which it is extracted by the liver. Although several studies suggested that it is the small, unbound fraction of bilirubin which interacts with hepatocytes and is removed from the circulation, recent experiments have been interpreted as suggesting that binding to albumin facilitates ligand uptake. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [3H]bilirubin was determined after injection as an equimolar complex with 125I-albumin, with 125I-ligandin, or free with only a [14C]sucrose reference. Uptake of 10 nmol of [3H]bilirubin was 67.5 ± 3.7% of the dose when injected with 125I-albumin, 67.4 ± 6.5% when injected with 125I-ligandin, and 74.9 ± 2.4% when injected with [14C]sucrose (P > 0.1). At 200 nmol, uptake fell to 46.4 ± 3.1% (125I-albumin) and 63.3 ± 3.4% ([14C]sucrose) of injected [3H]bilirubin (P < 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [3H]bilirubin was injected simultaneously with equimolar 125I-albumin and a [14C]sucrose reference, there was no delay in 125I-albumin transit as compared with that of [14C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon.

Original languageEnglish (US)
Pages (from-to)718-723
Number of pages6
JournalJournal of Clinical Investigation
Volume72
Issue number2
StatePublished - 1983
Externally publishedYes

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Bilirubin
Albumins
Liver
Sucrose
Glutathione Transferase
Fluorocarbons
Cell Surface Receptors
Hepatocytes
Ligands
Serum-Free Culture Media

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding. / Stollman, Y. R.; Gartner, U.; Theilmann, L.; Ohmi, N.; Wolkoff, Allan W.

In: Journal of Clinical Investigation, Vol. 72, No. 2, 1983, p. 718-723.

Research output: Contribution to journalArticle

Stollman, Y. R. ; Gartner, U. ; Theilmann, L. ; Ohmi, N. ; Wolkoff, Allan W. / Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding. In: Journal of Clinical Investigation. 1983 ; Vol. 72, No. 2. pp. 718-723.
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abstract = "Bilirubin uptake by the liver is a rapid process of high specificity that has kinetic characteristics which suggest carrier-mediation. In the circulation, bilirubin is readily bound to albumin, from which it is extracted by the liver. Although several studies suggested that it is the small, unbound fraction of bilirubin which interacts with hepatocytes and is removed from the circulation, recent experiments have been interpreted as suggesting that binding to albumin facilitates ligand uptake. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [3H]bilirubin was determined after injection as an equimolar complex with 125I-albumin, with 125I-ligandin, or free with only a [14C]sucrose reference. Uptake of 10 nmol of [3H]bilirubin was 67.5 ± 3.7{\%} of the dose when injected with 125I-albumin, 67.4 ± 6.5{\%} when injected with 125I-ligandin, and 74.9 ± 2.4{\%} when injected with [14C]sucrose (P > 0.1). At 200 nmol, uptake fell to 46.4 ± 3.1{\%} (125I-albumin) and 63.3 ± 3.4{\%} ([14C]sucrose) of injected [3H]bilirubin (P < 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [3H]bilirubin was injected simultaneously with equimolar 125I-albumin and a [14C]sucrose reference, there was no delay in 125I-albumin transit as compared with that of [14C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon.",
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T1 - Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding

AU - Stollman, Y. R.

AU - Gartner, U.

AU - Theilmann, L.

AU - Ohmi, N.

AU - Wolkoff, Allan W.

PY - 1983

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N2 - Bilirubin uptake by the liver is a rapid process of high specificity that has kinetic characteristics which suggest carrier-mediation. In the circulation, bilirubin is readily bound to albumin, from which it is extracted by the liver. Although several studies suggested that it is the small, unbound fraction of bilirubin which interacts with hepatocytes and is removed from the circulation, recent experiments have been interpreted as suggesting that binding to albumin facilitates ligand uptake. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [3H]bilirubin was determined after injection as an equimolar complex with 125I-albumin, with 125I-ligandin, or free with only a [14C]sucrose reference. Uptake of 10 nmol of [3H]bilirubin was 67.5 ± 3.7% of the dose when injected with 125I-albumin, 67.4 ± 6.5% when injected with 125I-ligandin, and 74.9 ± 2.4% when injected with [14C]sucrose (P > 0.1). At 200 nmol, uptake fell to 46.4 ± 3.1% (125I-albumin) and 63.3 ± 3.4% ([14C]sucrose) of injected [3H]bilirubin (P < 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [3H]bilirubin was injected simultaneously with equimolar 125I-albumin and a [14C]sucrose reference, there was no delay in 125I-albumin transit as compared with that of [14C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon.

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