The hepatic galactosyl receptor system: Two different ligand dissociation pathways are mediated by distinct receptor populations

After internalization of ¹²⁵I-asialo-orosomucoid (ASOR) by isolated rat hepatocytes, ligand dissociates by two kinetically distinct pathways (Oka and Weigel, J. Biol. Chem. 257, 10,253, 1983). These slow and fast dissociation pathways correspond to two functionally different subpopulations of cell surface galactosyl receptors designated, respectively, State 1 and State 2 receptors. Freshly isolated cells or cells equilibrated below 24°C express only State 1 receptors. Cells equilibrated at 37°C express both State 1 and State 2 receptors. Ligand dissociation after internalization of surface-bound ¹²⁵I-ASOR was measured using the permeabilizing detergent, digitonin. The slow dissociation pathway was mediated by State 1 receptors and was the only pathway expressed by cells which were freshly isolated or had been equilibrated at 24°C. State 2 receptors are expressed at temperatures above about 20°C, and both the fast and slow dissociation pathways occurred in cells equilibrated at 37°C. State 2 receptors therefore mediate the rapid dissociation pathway. Dissociation and subsequent degradation of specifically bound ligand routed in either pathway were complete, respectively, within 3 and 6 hrs.