Tolleshaug H, Berg T, Holte K
Biochim Biophys Acta. 1982 Jan 12;714(1):114-21. doi: 10.1016/0304-4165(82)90132-5.
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.
研究了包括普鲁卡因和丁卡因在内的局部麻醉剂以及一些相关胺类化合物（如丹磺酰尸胺）对分离的肝细胞中去唾液酸糖蛋白摄取和降解的影响。0.5 mM的丁卡因或丹磺酰尸胺可将摄取率降低至对照值的18 - 19%；其他胺类的效果较差。丁卡因和丹磺酰尸胺的作用方式都是降低细胞的表面结合能力以及降低表面结合的去唾液酸糖蛋白的内化速率。所有影响摄取的化合物，包括丹磺酰尸胺，也都降低了降解速率。这种效应可以与它们对摄取的影响分开研究。一般来说，降低降解所需的浓度是导致摄取降低的浓度的0.5 - 0.25倍。尽管发现丁卡因、利多卡因和丹磺酰尸胺在溶酶体中积累，但通过在蔗糖梯度中进行等密度离心研究得出结论，这三种化合物均抑制内吞蛋白从内吞小泡向溶酶体的转移速率。这种效应可能是由于内吞小泡与溶酶体之间的融合速率降低所致。
