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A carrier‐protein receptor is not a prerequisite for avid hepatic elimination of highly bound compounds: A study of propranolol elimination by the isolated perfused rat liver
Author(s) -
Jones D. Brian,
Ching Michael S.,
Smallwood Richard A.,
Morgan Denis J.
Publication year - 1985
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840050411
Subject(s) - albumin , hepatocyte , propranolol , medicine , receptor , chemistry , endocrinology , serum albumin , free fraction , biochemistry , plasma protein binding , biology , in vitro
The highly efficient hepatic extraction of propranolol by the isolated perfused rat liver does not diminish when albumin binding is increased from 30 to 75%. One possible explanation of this insensitivity of propranolol uptake to changes in albumin binding is the mediation of uptake of bound ligand by an albumin receptor on the hepatocyte as postulated for oleate, taurocholic acid and rose bengal. To test this hypothesis, the hepatic extraction of propranolol was studied in the isolated perfused rat liver using α 1 ‐acid glycoprotein, which lacks a hepatocyte receptor, as the carrier protein in the perfusate rather than albumin. Livers were perfused with a medium containing propranolol (4 μ M ) and varying concentrations of α 1 ‐acid glycoprotein (0 to 25 μ M ). Hepatic extraction of propranolol was very high (0.990 ± 0.006; mean ± S.D.) and did not alter significantly despite an increase in bound fraction from 0.2 to 0.8, thus closely paralleling the findings when albumin is the carrier protein. This result indicates that bound propranolol is efficiently cleared by the liver, presumably by a “free intermediate” mechanism, in the absence of a specific carrier‐protein receptor on the hepatocyte. This study does not, therefore, support the albumin receptor hypothesis.