Uptake of Vinca Alkaloids into Mammalian Nerve and its Subcellular Components

Publisher Website
Google Scholar
Abstract
Three Vinca alkaloids, vinblastine (VLB), vincristine (VCR) and vindesine (VDS), affect axoplasmic transport to differnt degrees, with VCR the most potent. The uptake of these 3 species by desheathed cat sciatic nerves in vitro was determined by using [3H]-labeled derivatives. In a sucrose medium, the uptake of VCR was 3-4 times greater than that of VLB and VDS, which is in accord with the neurotoxicity of VCR. Uptake of VCR was dependent on Ca2+ concentration in the medium. Removal of Ca2+ from the incubation medium reduced the uptake of VCR, without having much effect on VLB or VDS uptake. The uptake of all 3 Vinca agents into nerve in a saline medium was about 50% of that in a sucrose medium, and elimination of Ca2+ from the saline incubation medium did not result in any significant change in uptake. High Ca2+ concentrations (100 mM) in the incubation medium, which cause a block of axoplasmic transport, did not change the total uptake of the Vinca alkaloids to any significant degree. The amount of labeled alkaloid found in the soluble fraction decreased by 50%. There was an increase in the amount present in the particulate fraction, caused, most likely, by an aggregation of vinca-binding components. The amount of VCR associated with tubulin-containing components isolated by gel filtration of the soluble fraction increased 2-fold when the nerves were exposed to a high-Ca2+ medium, as might be expected of a microtubule disassembly. Exposure of the nerve to low temperatures (0.degree.-4.degree. C) for 90 min did not show any effect on the total uptake of Vinca alkaloids.