Seiler N, Sarhan S, Roth-Schechter B F
Neurochem Res. 1984 Jul;9(7):871-86. doi: 10.1007/BF00964520.
The possible role of polyamines in the development of isolated neuroblasts from the cerebral cortex of embryonic chick brain was studied by means of three enzyme activated irreversible inhibitors of ornithine decarboxylase. alpha-Difluoromethylornithine (MDL 71782) showed no effects on development at doses which depleted dramatically neuronal putrescine and spermidine levels. In contrast, the two other inhibitors, (E)-alpha-(fluoromethyl)dehydroputrescine (MDL 72197) and 6-heptyne-2,5-diamine (MDL 72175) blocked the formation of neuronal outgrowths completely at 100 microM and higher concentrations. Their effects on neuronal polyamines differed at this concentration considerably. The growth inhibitory effect of the ornithine decarboxylase inhibitors was in all cases reversible: cells which were grown after 3 days of exposure to the drugs in normal medium produced neuronal networks. The presence of putrescine at 10 microM concentration in the culture medium prevented the growth inhibitory effect of 100 microM concentrations of the drugs. This concentration of putrescine was not only capable of preventing, but also of reversing growth inhibition by the ornithine decarboxylase inhibitors. Although the cellular polyamine levels were not correlated with the morphological development of chick embryo cortical neurons, the present study leaves no doubt that putrescine plays an essential role in neuronal differentiation.
利用三种鸟氨酸脱羧酶的酶激活不可逆抑制剂，研究了多胺在鸡胚大脑皮层分离神经母细胞发育过程中可能发挥的作用。α-二氟甲基鸟氨酸（MDL 71782）在能显著降低神经元腐胺和亚精胺水平的剂量下，对细胞发育没有影响。相比之下，另外两种抑制剂，（E）-α-（氟甲基）脱氢腐胺（MDL 72197）和6-庚炔-2,5-二胺（MDL 72175）在100微摩尔及更高浓度时完全阻断了神经元突起的形成。在此浓度下，它们对神经元多胺的影响有很大差异。鸟氨酸脱羧酶抑制剂的生长抑制作用在所有情况下都是可逆的：在药物处理3天后于正常培养基中培养的细胞产生了神经元网络。培养基中10微摩尔浓度的腐胺可防止100微摩尔浓度药物的生长抑制作用。这种浓度的腐胺不仅能够预防，而且能够逆转鸟氨酸脱羧酶抑制剂对生长的抑制作用。尽管细胞内多胺水平与鸡胚皮质神经元的形态发育并无关联，但本研究无疑表明腐胺在神经元分化过程中起着至关重要的作用。
