Dynamic determination of kinetic parameters for the interaction between polypeptide hormones and cell-surface receptors in the perfused rat liver by the multiple-indicator dilution method

Journal Article · Tue Nov 01 00:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.21.8355· OSTI ID:5413645

Sato, H; Sugiyama, Y; Sawada, Y; Iga, T; Sakamoto, S; Fuwa, T; Hanano, M ^[1]

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1. Univ. of Tokyo (Japan)

Hepatic elimination of epidermal growth factor (EGF) via receptor-mediated endocytosis was studied by a multiple-indicator dilution method in the isolated perfused rat liver, in which cell polarity and spatial organization are maintained. In this method EGF was given with inulin, an extracellular reference, as a bolus into the portal vein, and dilution curves of both compounds in the hepatic vein effluent were analyzed. Analysis of the dilution curve for EGF, compared with that for somatostatin, which showed no specific binding to isolated liver plasma membranes, resulted as follows: (i) both extraction ratio and distribution volume of {sup 125}I-labeled EGF decreased as the injected amount of unlabeled EGF increased; (ii) the ratio plot of the dilution curve for EGF exhibited an upward straight line initially for a short period of time, whereas the ratio plot of somatostatin gradually decreased. The multiple-indicator dilution method was used for other peptides also. Insulin and glucagon, known to have hepatocyte receptors, behaved similarly to EGF in shape of their ratio plots. The kinetic parameters calculated by this analysis were comparable with reported values obtained by in vitro direct binding measurements at equilibrium using liver homogenates. They conclude that the multiple-indicator dilution method is a good tool for analyzing the dynamics of peptide hormones-cell-surface receptor interaction under a condition in which spatial architecture of the liver is maintained.

• OSTI ID: 5413645
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:21; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GROWTH FACTORS
EXCRETION
PEPTIDE HORMONES
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
DYNAMIC FUNCTION STUDIES
INULIN
IODINE 125
LIVER
PERFUSED TISSUES
RATS
RECEPTORS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
POLYSACCHARIDES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SACCHARIDES
TISSUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques