Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding
Journal Article
·
· J. Clin. Invest.; (United States)
Bilirubin uptake by the liver has kinetic characteristics which suggest carrier-mediation. Bilirubin is readily bound to albumin. 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 (/sup 3/H)bilirubin was determined after injection as an equimolar complex with /sup 125/I-albumin, with /sup 125/I-ligandin, or free with only a (/sup 14/C)sucrose reference. Uptake of 10 nmol of (/sup 3/H)bilirubin was 67.5 +/- 3.7% of the dose when injected with /sup 125/I-albumin, 67.4 +/- 6.5% when injected with /sup 125/I-ligandin, and 74.9 +/- 2.4% when injected with (/sup 14/C)sucrose (P greater than 0.1). At 200 nmol, uptake fell to 46.4 +/- 3.1% (/sup 125/I-albumin) and 63.3 +/- 3.4% ((/sup 14/C)sucrose) of injected (/sup 3/H)bilirubin (P less than 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When (/sup 3/H)bilirubin was injected simultaneously with equimolar /sup 125/I-albumin and a (/sup 14/C)sucrose reference, there was no delay in /sup 125/I-albumin transit as compared with that of (/sup 14/C)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.
- Research Organization:
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
- OSTI ID:
- 5606883
- Journal Information:
- J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 72:2; ISSN JCINA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BILIRUBIN
BIOCHEMICAL REACTION KINETICS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL PREPARATION
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIVER
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PERFUSED ORGANS
PIGMENTS
PROTEINS
PYRROLES
RADIOCHEMISTRY
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYNTHESIS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BILIRUBIN
BIOCHEMICAL REACTION KINETICS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL PREPARATION
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIVER
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PERFUSED ORGANS
PIGMENTS
PROTEINS
PYRROLES
RADIOCHEMISTRY
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYNTHESIS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES