Pongrac J L, Rylett R J
Department of Physiology, University of Western Ontario, London, Canada.
J Neurochem. 1996 Feb;66(2):804-10. doi: 10.1046/j.1471-4159.1996.66020804.x.
Nerve growth factor (NGF) treatment of primary cultures of embryonic day 17 rat basal forebrain differentially altered activity of choline acetyltransferase (ChAT) and high-affinity choline transport; ChAT specific activity was increased by threefold in neurons grown in the presence of NGF for between 4 and 8 days, whereas high-affinity choline transport activity was not changed relative to control. Dose-response studies revealed that enhancement of neuronal ChAT activity occurred at low concentrations of NGF with an EC50 of 7 ng/ml, with no enhancement of high-affinity choline transport observed at NGF concentrations up to 100 ng/ml. In addition, synthesis of acetylcholine (ACh) and ACh content in neurons grown in the presence of NGF for up to 6 days was increased significantly compared with controls. These results suggest that regulation of ACh synthesis in primary cultures of basal forebrain neurons is not limited by provision of choline by the high-affinity choline transport system and that increased ChAT activity in the presence of NGF without a concomitant increase in high-affinity choline transport is sufficient to increase ACh synthesis. This further suggests that intracellular pools of choline, which do not normally serve as substrate for ACh synthesis, may be made available for ACh synthesis in the presence of NGF.
用神经生长因子（NGF）处理胚胎第17天大鼠基底前脑的原代培养物，可使胆碱乙酰转移酶（ChAT）的活性和高亲和力胆碱转运发生不同程度的改变；在NGF存在下培养4至8天的神经元中，ChAT的比活性增加了两倍，而高亲和力胆碱转运活性相对于对照组没有变化。剂量反应研究表明，低浓度的NGF即可增强神经元ChAT的活性，其半数有效浓度（EC50）为7 ng/ml，在高达100 ng/ml的NGF浓度下，未观察到高亲和力胆碱转运增强。此外，与对照组相比，在NGF存在下培养长达6天的神经元中，乙酰胆碱（ACh）的合成和ACh含量显著增加。这些结果表明，基底前脑神经元原代培养物中ACh合成的调节不受高亲和力胆碱转运系统提供胆碱的限制，并且在NGF存在下ChAT活性增加而高亲和力胆碱转运没有相应增加就足以增加ACh的合成。这进一步表明，通常不作为ACh合成底物的细胞内胆碱池，在NGF存在下可能可用于ACh的合成。
