title: Effects of local anesthetics and related compounds on the endocytosis and catabolism of asialo-glycoproteins in isolated hepatocytes.
abstract: The effects of local anesthetics, including procaine and dibucaine, and some related amine compounds, such as dansyl-cadaverine, were studied with respect to their effects on the uptake and degradation of asialo-glycoproteins in isolated hepatocytes. 0.5 mM of either dibucaine or dansyl-cadaverine reduced the rates of uptake to 18-19% of control value; other amines were less effective. Dibucaine and dansyl-cadaverine both acted by reducing the surface binding capacity of the cells as well as by reducing the rate of internalization of surface-bound asialo-glycoprotein. All of the compounds that affected the uptake, including dansyl-cadaverine, also reduced the rate of degradation. This effect could be studied separately from their effect on uptake. The concentrations that were required in order to reduce degradation were, in general 0.5-0.25 of those which caused a reduction in the uptake. Even though dibucaine, lidocaine and dansyl-cadaverine were found to accumulate in the lysosomes, it was concluded from studies with isopycnic centrifugation in sucrose gradients that all three compounds inhibited the rate of transfer of endocytosed protein from endocytic vesicles to lysosomes. This effect could be due to a reduced rate of fusion between endocytic vesicles and lysosomes.
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001212:Asialoglycoproteins; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D001212:Asialoglycoproteins; D006023:Glycoproteins; D013748:Tetracaine; D011343:Procaine; C008542:monodansylcadaverine; D003992:Dibucaine; D002103:Cadaverine