ABSTRACT
Equilibrium microdialysis of [3H]acetyltaxol against different tubulin assemblies showed that: (i) the binding capacity of tubulin does not depend on the temperature; (ii) two classes of 'polymers' exist, with respect to Ac-taxol binding. Some of them (plaques, complex cylinders induced with some polycations and spirals made with rhazinilam) bound Ac-taxol, as do normal microtubules. In contrast, spirals formed with vinblastine and griseofulvin, rings made with polycations and complex cylinders induced with spermine do not bind Ac-taxol as is the case with free tubulin.
Subject(s)
Alkaloids/metabolism , Brain Chemistry , Paclitaxel/analogs & derivatives , Taxoids , Tubulin/metabolism , Alkaloids/pharmacology , Animals , Dialysis , Dimethyl Sulfoxide/pharmacology , Dimethylformamide/pharmacology , Griseofulvin/pharmacology , Indolizines , Lactams , Macromolecular Substances , Microscopy, Electron , Polylysine/pharmacology , Protamines/pharmacology , Sheep , Spermine/pharmacology , Sulfates/pharmacology , Temperature , Vinblastine/pharmacology , Zinc/pharmacology , Zinc SulfateABSTRACT
The effect of taxol on microtubule proteins at 0 degrees C is controversial. In order to determine if taxol is unable to bind to unassembled tubulin, as has been hypothesized, the binding of [3H]acetyl taxol has been studied using equilibrium microdialysis. Ac-taxol bound to microtubules at 37 degrees C and the binding remained stable when the temperature was lowered to 0 degrees C. Ac-taxol bound also at 0 degrees C to microtubules stabilized with rhazinilam. In contrast, there was no binding of Ac-taxol to unassembled tubulin, either free tubulin at 0 degrees C or tubulin, complexed with several microtubule poisons, at 0 and 37 degrees C.
