The work carried out during the course of this year represents a continuation of earlier studies designed to clarify the functional role of the hepatic receptor for asialoglycoproteins and to establish the biochemical mechanisms involved in receptor modulation. Using the human hepatoblastoma cell line HepG2 as a model system, it was found that incubation of these cells in the presence of 10 mM N-Acetyl-D- mannosamine markedly increased the normal complement of cell surface sialic acid with resultant up modulation in the activity of the asialoglycoprotein receptor. A second and unexpected result was the threefold stimulation in fucose incorporation, indicative of a complex metabolic interaction between these two inversely related sugars. Thirdly, an examination of the role of cGMP, as second messenger, revealed that it restored normal ligand binding but was unable to produce the hyperbinding activity produced by high levels of glucose; cAMP blocked the effect of cGMP. The significance of the above findings relates to analogous changes reported in the livers of diabetic rats.
