Nocodazole action on tubulin assembly, axonal ultrastructure and fast axoplasmic transport.

The action of a synthetic antitubulin agent, nocodazole, on tubulin self-assembly, preformed microtubules, fast axoplasmic transport and axonal ultrastructure was studied. Nocodazole completely blocks the self-assembly of tubulin containing or lacking associated proteins. This inhibition is readily reversible. At similar concentrations, nocodazole also depolymerizes preformed microtubules in vitro. Fast axoplasmic transport in cat vagus nerve is disrupted by bathing the nerve fivers in a medium containing 10 micrometer nocodazole for periods of 2.5 hr or longer. A 4-hr exposure results in extensive inhibition. The nocodazole action on fast axoplasmic transport appears to be reversible but with a high degree of variability. After 2.5 hr of exposure to 10 micrometers nocodazole, there is a slight decrease in axonal microtubules and an increase in 10 nm neurofilaments. A 4 hr exposure results in a marked reduction in microtubules. These results suggest that nocodazole has a mode of action similar to other antimicrotubule agents.