Buck H, Winter J
Sandoz Institute for Medical Research, London, England.
J Neurochem. 1996 Jul;67(1):345-51. doi: 10.1046/j.1471-4159.1996.67010345.x.
K252a, an inhibitor of trk phosphorylation and nerve growth factor signal transduction in PC12 cells, blocked nerve growth factor-induced responses in cultured adult rat dorsal root ganglion sensory neurones. The nerve growth factor-dependent appearance of capsaicin sensitivity and accumulation of the neuropeptide substance P were inhibited when dorsal root ganglion neurones were grown in the presence of low concentrations (100 nM) of K252a. At higher concentrations (3 microM), however, K252a stimulated the development of capsaicin sensitivity and the accumulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. These results may explain the apparent paradox in the literature that some groups show a blocking effect of K252a on nerve growth factor-dependent survival of dorsal root ganglion sensory neurones, whereas other report that K252a can substitute for nerve growth factor or other trophic factors and promote neuronal survival.
K252a是一种PC12细胞中trk磷酸化和神经生长因子信号转导的抑制剂，它能阻断培养的成年大鼠背根神经节感觉神经元中神经生长因子诱导的反应。当背根神经节神经元在低浓度（100 nM）的K252a存在下生长时，辣椒素敏感性的神经生长因子依赖性出现和神经肽P物质的积累受到抑制。然而，在较高浓度（3 μM）时，即使在没有神经生长因子的情况下，K252a也能刺激辣椒素敏感性的发展和P物质的积累。因此，通过使用广泛的剂量范围，我们表明K252a可以抑制或模拟神经生长因子对感觉神经元的作用。这些结果可能解释了文献中明显的矛盾之处，即一些研究小组表明K252a对背根神经节感觉神经元的神经生长因子依赖性存活有阻断作用，而其他研究则报道K252a可以替代神经生长因子或其他神经营养因子并促进神经元存活。
