Donoso J A, Watson D F, Heller-Bettinger I E, Samson F E
Cancer Res. 1978 Jun;38(6):1633-7.
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 micron maytansine. A reduction in the number of microtubules and a partial blockage of fast axoplasmic transport was observed at 20 and 100 micron maytansine; at 10 micron 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.
美登素是一种目前正处于抗肿瘤药物临床试验阶段的安莎大环内酯类化合物，它是微管聚合的强效抑制剂。由于微管参与轴浆运输，因此对美登素对运输的影响进行了研究。在体外暴露于美登素的猫的迷走神经中，研究了蛋白质的快速轴浆运输和轴突超微结构。将氚标记的亮氨酸微量注射到结状神经节中；在掺入蛋白质2小时后，取出神经进行运输和超微结构研究，并在含有100、20、10、5或1微米美登素的 Krebs-Ringer 溶液中孵育2.5小时。在20和100微米美登素浓度下观察到微管数量减少和快速轴浆运输部分受阻；在10微米时未观察到可检测到的变化。这些发现表明，体外美登素会诱导神经原纤维成分的改变，并伴有快速轴浆运输的部分受阻。
