Greene L A, Volonté C, Chalazonitis A
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
J Neurosci. 1990 May;10(5):1479-85. doi: 10.1523/JNEUROSCI.10-05-01479.1990.
Past studies have shown that purine analogs block certain, but not all, responses of cultured rat PC12 pheochromocytoma cells to nerve growth factor (NGF). In the present work, newborn rat sympathetic and sensory neurons were exposed to NGF in the presence or absence of the purine analogs 6-thioguanine and 2-aminopurine. These compounds reversibly suppressed NGF-dependent neurite outgrowth by the neurons and did so at concentrations comparable to those effective on PC12 cells. In contrast to their effects on neurites, neither compound significantly blocked NGF-promoted neuronal survival. Similar effects were seen with cultures of chick embryo sympathetic ganglia. These findings show that purine analog effects on NGF responses can be extended to mammalian and avian neurons. Moreover, the differential effects of the analogs on neurite outgrowth and survival indicate that these 2 actions of NGF can be dissected from one another and may represent different mechanistic pathways.
以往的研究表明，嘌呤类似物可阻断培养的大鼠嗜铬细胞瘤PC12细胞对神经生长因子（NGF）的某些而非全部反应。在本研究中，新生大鼠的交感神经元和感觉神经元在有或没有嘌呤类似物6-硫鸟嘌呤和2-氨基嘌呤存在的情况下暴露于NGF。这些化合物可逆地抑制神经元的NGF依赖性神经突生长，且抑制浓度与对PC12细胞有效的浓度相当。与它们对神经突的作用相反，这两种化合物均未显著阻断NGF促进的神经元存活。鸡胚交感神经节培养物也观察到类似的效果。这些发现表明，嘌呤类似物对NGF反应的影响可扩展至哺乳动物和鸟类神经元。此外，类似物对神经突生长和存活的不同影响表明，NGF的这两种作用可以相互分离，可能代表不同的机制途径。
