Park S K, Grzybicki D, Lin H L, Murphy S
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242.
Neuropharmacology. 1994 Nov;33(11):1419-23. doi: 10.1016/0028-3908(94)90044-2.
Nitric oxide is produced in the CNS by both constitutive and inducible isoforms of nitric oxide synthase. Once nitric oxide synthase is transcriptionally induced in astrocytes in vitro, these cells release large amounts of nitric oxide tonically. Glial cell-derived nitric oxide can be toxic to neurons and oligodendrocytes and is implicated in a variety of neuropathologies, suggesting that the expression of nitric oxide synthase in glia must be finely regulated. From northern and western blot analysis we have identified various agents (transforming growth factor-beta, nitric oxide, receptor agonists) that modulate cytokine-induced expression of nitric oxide synthase mRNA in astrocytes. This suggests that the magnitude and duration of nitric oxide production from activated astrocytes in vivo may be determined by signals from adjacent neurons and microglial cells.
一氧化氮在中枢神经系统中由一氧化氮合酶的组成型和诱导型同工型产生。一旦在体外星形胶质细胞中转录诱导一氧化氮合酶,这些细胞就会持续释放大量一氧化氮。神经胶质细胞衍生的一氧化氮对神经元和少突胶质细胞可能有毒性,并与多种神经病理学有关,这表明神经胶质细胞中一氧化氮合酶的表达必须受到精细调节。通过Northern印迹和Western印迹分析,我们确定了各种可调节细胞因子诱导的星形胶质细胞中一氧化氮合酶mRNA表达的因子(转化生长因子-β、一氧化氮、受体激动剂)。这表明体内活化星形胶质细胞产生一氧化氮的量和持续时间可能由相邻神经元和小胶质细胞发出的信号决定。