Influence of albumin on the hepatic uptake of unconjugated bilirubin.

1. The initial distiibution volumes of [3H]bilirubin in six adult subjects were equivalent to those of "I-labelled albumin following simultaneous intravenous injection of both compounds. However, the initial rate of loss of [3H]bilirubin from plasma was seven to thirty times faster than that of 1311-labelled albumin. 2. In vitro uptake of [3H]bilirubin by Gunn rat liver slices occurred at a rate three times faster than could be accounted for by movement linked with albumin. 3. There was no in vitro transfer of [14C]bilirubin from albumin to the organic anion-binding proteins of rat liver cytosol. Instead, albumin was shown to strip [14C]bilirubin from these proteins. 4. When albumin, to which [14C]bilirubin had been bound, was precipitated with anti-albumin antibody, [14C]bilirubin was recovered completely in the supernatant, indicating that unconjugated bilirubin may be readily separated from albumin if albumin interacts with another macromolecule. 5. These results indicated that unconjugated bilirubin is separated from albumin prior to its uptake by the hepatic cell, rather than the entire albumin-bilirubin complex entering the hepatocyte. The data suggest that the uptake mechanism probably requires the participation of the plasma membrane.