title: Evidence for transmembrane modulation of the ligand-binding site of the hepatocyte galactose/N-acetylgalactosamine-specific receptor.
abstract: The ligand-binding activity of the galactose/N-acetylgalactosamine-specific receptor (Gal/GalNAc receptor) present on the surface of hepatocytes can be modulated under a number of conditions in the intact cell. The carboxylic acid ionophores monensin and nigericin inhibit endocytosis by the Gal/GalNAc receptor in a concentration-dependent manner. Monensin at a concentration of 100 microM reduces the number of binding sites for asialo-orosomucoid and a tri-branched glycopeptide (F2) 5-10-fold; however, the number of Gal/GalNAc receptor subunits detected at the cell surface by a competitive radioimmunoassay and by immunoprecipitation of surface labeled receptor is not significantly altered. Replacement of NaCl in the medium with either N-methylglucamine or sorbitol to isotonicity also inhibits binding and endocytosis. The monensin, nigericin, N-methylglucamine, and sorbitol treatments have in common the ability to alkalinize the cytosol of the hepatocyte. None of these agents has any effect on binding by the isolated Gal/GalNAc receptor nor is the intracellular pH shift of such a magnitude that it would alter binding by the isolated Gal/GalNAc receptor. This has led us to conclude that the ligand-binding properties of the Gal/GalNAc receptor at the cell surface can be modulated in a transmembrane fashion by events other than those involving pH or Ca2+ regulation at the ligand-binding site itself. Such transmembrane modulation of ligand binding by the Gal/GalNAc receptor may provide a rapid and efficient mechanism for mediating ligand release and immediate return of the receptor to the cell surface.
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000187:drug effects; D005690:Galactose / Q000378:metabolism; D006096:Gramicidin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008536:Meglumine / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic; D013012:Sorbitol / Q000494:pharmacology; D013696:Temperature
chemical_list: D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C037045:galactose-N-acetylgalactosamine receptor; D006096:Gramicidin; D013012:Sorbitol; D008536:Meglumine; D008985:Monensin; D000116:Acetylgalactosamine; D005690:Galactose