Kano T, Shimizu-Sasamata M, Huang P L, Moskowitz M A, Lo E H
Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Charlestown 02129, USA.
Neuroscience. 1998 Oct;86(3):695-9. doi: 10.1016/s0306-4522(98)00179-1.
Nitric oxide serves as a diffusible messenger within the neuronal networks of the brain. Recent studies have suggested that nitric oxide may amplify neurotransmitter release via its ability to diffuse in a retrograde manner from postsynaptic to presynaptic neurons. Two isoforms of nitric oxide synthase may be present in neurons: Type I nitric oxide synthase (neuronal isoform) and Type III nitric oxide synthase (endothelial isoform). In this study, we examined the role of nitric oxide as an amplifier of neurotransmitter release by using K+ and N-methyl-D-aspartate stimulations via microdialysis probes located in cortex, striatum, and hippocampus. We compared responses obtained in wild-type mice versus knockout mice deficient in either neuronal isoform of nitric oxide synthase or endothelial isoform of nitric oxide synthase gene expression. No significant differences in glutamate and GABA release were observed between knockout mice and wild-type mice after K+ stimulations. In contrast, N-methyl-D-aspartate-stimulated glutamate release in cortex was significantly reduced in the neuronal NOS knockout mice, and N-methyl-D-aspartate-stimulated GABA release was significantly reduced in all brain regions of endothelial NOS knockout mice. These data suggest that the two nitric oxide synthase isoforms, most likely due to their specific neuronal localizations, may serve different roles in the modulation of excitatory versus inhibitory neurotransmission in mammalian brain.
一氧化氮作为一种可扩散的信使分子，存在于大脑的神经网络中。最近的研究表明，一氧化氮可能通过其从突触后神经元向突触前神经元逆行扩散的能力来放大神经递质的释放。神经元中可能存在两种一氧化氮合酶亚型：I型一氧化氮合酶（神经元亚型）和III型一氧化氮合酶（内皮亚型）。在本研究中，我们通过位于皮层、纹状体和海马体的微透析探针，利用钾离子和N-甲基-D-天冬氨酸刺激，研究了一氧化氮作为神经递质释放放大器的作用。我们比较了野生型小鼠与一氧化氮合酶神经元亚型或内皮亚型基因表达缺陷的基因敲除小鼠的反应。钾离子刺激后，基因敲除小鼠和野生型小鼠之间的谷氨酸和γ-氨基丁酸释放没有显著差异。相比之下，神经元型一氧化氮合酶基因敲除小鼠皮层中N-甲基-D-天冬氨酸刺激的谷氨酸释放显著减少，内皮型一氧化氮合酶基因敲除小鼠所有脑区中N-甲基-D-天冬氨酸刺激的γ-氨基丁酸释放显著减少。这些数据表明，两种一氧化氮合酶亚型，很可能由于它们特定的神经元定位，在调节哺乳动物大脑中的兴奋性与抑制性神经传递中可能发挥不同作用。
