Hepatic Accumulation and Intracellular Binding of Conjugated Bilirubin

Abstract

A B S T R A C T After the intravenous injection of un

Identification, Purification, and Partial Characterization of an Organic Anion Binding Protein from Rat Liver Cell Plasma Membrane

“…The hepatic uptake of bilirubin and BSP is rapid. After the intravenous injection of tracer amounts of [3H]bilirubin or [35S]BSP in rats, -40% of injected radioactivity is present within the liver 1.5 min later (2,(4)(5)(6). In the isolated perfused rat liver, 30 '251-albumin is injected simultaneously, all 1251 is recovered in the hepatic vein effluent confirming that albumin does not accompany bilirubin or BSP into the liver cell (7,8).…”

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

“…BR, however, is not a substrate for glutathione conjugation. The binding to GSTs reduces the efflux of BR from hepatocytes increasing its net uptake (Kamisaka et al, 1975;Wolkoff et al, 1978Wolkoff et al, , 2012. BR is then converted into mono-and di-glucuronide predominantly by a single uridine diphosphoglucuronate glucuronosyltransferase (UGTs) isoform, UGT1A1 (Bosma et al, 1994).…”

“…While both strains are widely used in drug metabolism studies, strain characteristics might explain differences in responsiveness to certain inducing agents. For example, differences in glutathione S-transferase activity (GST) may alter net uptake of BR by hepatocytes (Wolkoff et al, 1978(Wolkoff et al, , 2012Higgins and Hayes, 2011). Furthermore, it has been reported that DBA/2 mice lack functional…”

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

“…Bilirubin is rapidly removed from the circulation and enters the hepatocyte, where it is conjugated with glucuronic acid and excreted into bile (3,4). Albumin does not enter the hepatocyte but remains in the circulation (5)(6)(7)(8)(9).…”