Peunova N, Enikolopov G
Cold Spring Harbor Laboratory, New York 11724.
Nature. 1993 Jul 29;364(6436):450-3. doi: 10.1038/364450a0.
Nitric oxide (NO) is a short-lived, highly reactive gas, which has been identified as a mediator in vasodilation, an active agent in macrophage cytotoxicity and neurotoxicity, and a neuro-transmitter in the central and peripheral nervous systems. Production of NO by neurons is critical for facilitated synaptic transmission in models of synaptic plasticity such as long-term potentiation and long-term depression, suggesting a role for NO as a retrograde messenger that could complete a hypothetical feedback loop by strengthening the connection between postsynaptic and presynaptic cells. We report here that although alone NO has no evident effect on transcription, it can act as an amplifier of calcium signals in neuronal cells. NO and Ca2+ action have to coincide in time for amplification to occur. Experiments with a series of simplified reporter genes in combination with specific recombinant protein kinase inhibitors suggest that induction of gene activity following NO-amplified calcium action involves protein kinase A-dependent activation of the transcription factor CREB.
一氧化氮（NO）是一种寿命短暂、反应性很强的气体，它已被确认为血管舒张的介质、巨噬细胞细胞毒性和神经毒性的活性剂，以及中枢和外周神经系统中的一种神经递质。在诸如长时程增强和长时程抑制等突触可塑性模型中，神经元产生NO对于促进突触传递至关重要，这表明NO作为一种逆行信使可能通过加强突触后和突触前细胞之间的连接来完成一个假设的反馈回路。我们在此报告，虽然单独的NO对转录没有明显影响，但它可以作为神经元细胞中钙信号的放大器。NO和Ca2+的作用必须在时间上重合才能发生放大。用一系列简化的报告基因结合特定的重组蛋白激酶抑制剂进行的实验表明，NO放大的钙作用后基因活性的诱导涉及转录因子CREB的蛋白激酶A依赖性激活。
