Nitric oxide in excitable tissues: Physiological roles and disease
Nitric oxide in excitable tissues: Physiological roles and disease
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DOI：
10.1172/jci119783
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发表时间：
1997-11-15
影响因子：
15.9
通讯作者：
Bredt, DS
中科院分区：
文献类型：
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作者：
Christopherson, KS;Bredt, DS
一氧化氮(NO)1是血管和免疫系统中一种独特的可扩散和反应的分子信使，这一发现促使人们寻找体内不存在的生物合成。NO很快在中枢和外周神经系统中大量存在(1-3个)。事实上，从L精氨酸中产生一氧化氮的一氧化氮合酶在大脑中的水平比其他任何组织中都要高，这有助于最初分离一氧化氮合酶蛋白和克隆一氧化氮合酶基因(4)。过去10年的深入研究已经确定，NO参与了与神经元相关的多种生理功能。在外周神经系统中，NO在调节胃肠动力、局部血流量和神经内分泌功能方面与经典的神经递质非常相似。在大脑中，一氧化氮起神经调节剂的作用，控制行为活动，影响记忆形成，并加强对痛苦刺激的反应。此外，可兴奋组织中的NO生物合成并不局限于神经元。最近的研究发现，骨骼肌是体内NO的主要来源(5，6)，其中NO既调节新陈代谢又调节肌肉收缩。兴奋性组织中NO的生物合成受到细胞内钙的增加的调节，细胞内钙的增加通过酶对钙调蛋白的依赖来激活一氧化氮合酶(7)。虽然神经和骨骼肌活动过程中合成的少量NO介导了生理功能，但过量的NO产生可以介导组织损伤。例如，在脑缺血期间产生的大量一氧化氮在不同形式的中风中调节神经元损伤(8)。在其他情况下，类似的NO介导的损伤也可能导致神经退行性变，包括帕金森氏病、肌萎缩侧索硬化症和亨廷顿病。NO信号在各种肌肉疾病中也受到干扰，特别是在杜氏肌营养不良症中，这些紊乱可能
The discovery of nitric oxide (NO) 1 as a uniquely diffusible and reactive molecular messenger in the vascular and immune systems motivated searches for NO biosynthesis throughout the body. NO was soon found in abundance in the central and peripheral nervous systems (1–3). Indeed, NO synthase (NOS), the enzyme that produces NO from L-arginine, occurs at higher levels in brain than in any other tissue, which facilitated the initial isolation of an NOS protein and cloning of an NOS cDNA (4). Intensive studies over the past 10 yr have determined that NO mediates diverse physiological functions associated with neurons. In the peripheral nervous system, NO acts much like a classical neurotransmitter in regulating gastrointestinal motility, regional blood flow, and neuroendocrine function. In the brain, NO acts as a neuromodulator to control behavioral activity, influence memory formation, and intensify responses to painful stimuli. Furthermore, NO biosynthesis in excitable tissues is not restricted to neurons. Recent studies have identified skeletal muscle as a major source for NO in the body (5, 6) where NO regulates both metabolism and muscle contractility.NO biosynthesis in excitable tissues is regulated by increases in intracellular calcium, which activate NOS through the enzyme’s dependence upon calmodulin (7). Although small amounts of NO synthesized during neural and skeletal muscle activity mediate physiological functions, excess NO production can mediate tissue injury. For example, large amounts of NO produced during periods of cerebral ischemia mediate neuronal injury in various forms of stroke (8). Similar NO-mediated damage may account for neurodegeneration in other conditions as well, including Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. NO signaling is also perturbed in various muscle diseases, particularly in Duchenne muscular dystrophy, and these derangements may