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Maytansine Action on Fast Axoplasmic Transport and the Ultrastructure of Vagal Axons¹

Ralph L. Smith Research Center [J. A. D., D. F. W., I. H-B., F. E. S.] and Department of Neurology [I. H-B.], University of Kansas Medical Center, Kansas City, Kansas 66103

Maytansine, an ansa macrolide now in clinical trials as an antineoplastic drug, is a potent inhibitor of microtubule polymerization. Since microtubules are involved in axoplasmic transport, the effect of maytansine on transport was examined. Fast axoplasmic transport of proteins and the axonal ultrastructure was studied in the vagus nerve of cats exposed in vitro to maytansine. Tritiated leucine was microinjected into the nodose ganglion; after 2 hr for incorporation into proteins, nerves were dissected out for transport and ultrastructural studies and incubated for 2.5 hr in Krebs-Ringer solution with 100, 20, 10, 5, or 1 µM maytansine. A reduction in the number of microtubules and a partial blockage of fast axoplasmic transport was observed at 20 and 100 µM maytansine; at 10 µM no detectable changes were observed. These findings show that maytansine in vitro induces alterations of the neurofibrillar elements concomitant with a partial blockage of fast axoplasmic transport.

¹ Supported in part by National Institute of Child Health and Human Development Grant HD-02528-12 and a grant from the Eli Lilly Co., Indianapolis, Ind.

² To whom requests for reprints should be addressed.

Received 11/23/77. Accepted 3/14/78.