Inhibition of neurite initiation and growth by taxol.

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Abstract
Sensory neurons from chick embryos were cultured in media containing the alkaloid taxon at cncentrations from 7 .times. 10-9-3.5 .times. 10-6 M. When plated at taxon concentrations > 7 .times. 10-8 M for 24 h, neurons have short broad extensions that do not elongate on the culture substratum. When actively growin neurites are expoed to these levels of taxol, neurite growth stops immediately and does not recommence. The broad processes of neurons cultured 24 h with taxol contain densely packed arrays of microtubules that loop back at the ends of the process. Neurofilaments are segregated from microtubules into bundles and tangled masses in these taxol-treated neurons. At the ends of neurites treated for 5 min with taxol, microtubules also turn and loop back abnormally toward the perikaryon. In the presence of 7 .times. 10-9 M taxol neurites do grow, although they are broader and less branched than normally. The neurites of these cells appear to have normal structure except for a large number of microtubules. Taxol probably stimulates microtubule polymerization in these cultured neurons. At high levels of the drug, this action inhibits neurite initiation and outgrowth by removing free tubulin from the cytoplasm and destroying the normal control of microtubule assembly in growing neurites. The rapid inhibition suggests that microtubule assembly may occurr at neurite tips. At lower concentrations, taxol may slightly enhance the mechanisms of microtubule assembly in neurons, and this alteration of normal process changes the morphogenetic properties of the growing neurites.