Nitric Oxide in the Nervous System

Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, Maryland 21205, USA.
Annual Review of Pharmacology (Impact Factor: 18.37). 02/1995; 35(1):213-33. DOI: 10.1146/
Source: PubMed


Nitric oxide (NO) has only recently been appreciated as a normal biologic substance with a role in signal transduction. It was first identified as endothelial-derived relaxing factor in blood vessels and as the mediator of the tumoricidal and bactericidal actions of macrophages. NO's role as a neural messenger may be even more prominent. Biosynthesis of NO involves oxidation of the guanidine group of arginine with stoichiometric formation of citrulline. NO synthase is one of the most extensively regulated enzymes in biology. In the periphery, NO is a likely transmitter of nonadrenergic, noncholinergic neurons. In the brain, NO neurons mediate action of glutamate acting at N-methyl-D-aspartate (NMDA) receptors. Excess release of NO appears to account for a major portion of neural damage following vascular stroke.

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    • "It is of interest to note that there was also a significant reduction in eNOS protein in the aged brain stem, although no age-related change in NOS activity was found in this region. It has been shown that the expression or synthesis of NOS proteins can be regulated independently of their activity (Zhang and Snyder, 1995). Taking the findings together, it appears that aging affects eNOS dramatically in both the brain stem and the spinal cord, although earlier studies have "
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    ABSTRACT: Accumulating evidence suggests that the metabolism of L-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine and its eight down-stream metabolites in the brain stem (pons and medulla) and the cervical spinal cord in 3 (young) and 22 (aged) months old male Sprague Dawley rats. Total NOS activity was significantly reduced with age in the spinal cord (but not brain stem), and there were no age-related changes in arginase activity in both regions. Western blot revealed decreased protein expression of endothelial NOS, but not neuronal NOS, with age in both regions. Furthermore, there were significantly decreased L-arginine, glutamate, GABA and spermine levels and increased putrescine and spermidine levels with age in both regions. Although the absolute concentrations of L-arginine and 6 metabolites were significantly different between the brain stem and spinal cord in both age groups, there were similar clusters between L-arginine and its three main metabolites (L-citrulline, L-ornithine and agmatine) in both regions, which changed as a function of age. These findings, for the first time, demonstrate the regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord. Future research is required to understand the functional significance of these changes and the underlying mechanisms.
    Neuroscience 08/2013; 252. DOI:10.1016/j.neuroscience.2013.08.002 · 3.36 Impact Factor
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    • "A wide range of animal studies were performed employing L-NMA to determine the physiological role of NO in immune (e.g., [17]), nervous (e.g., [19]), and cardiovascular (e.g., [18] [28]) systems and particularly as a potential treatment of septic shock to reverse sepsisassociated hypotension. Primarily, Kilbourn et al. found that L-NMA (20 mg/kg, i.v.) prevented hypotension in septic dogs in an arginine-reversible manner, though L-NMA increased blood pressure in control animals [29] [30]. "
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    ABSTRACT: In the past three decades, nitric oxide has been well established as an important bioactive molecule implicated in regulation of cardiovascular, nervous, and immune systems. Therefore, it is not surprising that much effort has been made to find specific inhibitors of nitric oxide synthases (NOS), the enzymes responsible for production of nitric oxide. Among the many NOS inhibitors developed to date, inhibitors based on derivatives and analogues of arginine are of special interest, as this category includes a relatively high number of compounds with good potential for experimental as well as clinical application. Though this group of inhibitors covers early nonspecific compounds, modern drug design strategies such as biochemical screening and computer-aided drug design have provided NOS-isoform-specific inhibitors. With an emphasis on major advances in this field, a comprehensive list of inhibitors based on their structural characteristics is discussed in this paper. We provide a summary of their biochemical properties as well as their observed effects both in vitro and in vivo. Furthermore, we focus in particular on their pharmacology and use in recent clinical studies. The potential of newly designed specific NOS inhibitors developed by means of modern drug development strategies is highlighted.
    Mediators of Inflammation 09/2012; 2012:318087. DOI:10.1155/2012/318087 · 3.24 Impact Factor
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    • "NO is involved in neurotransmitter release [4, 5] and synaptic plasticity throughout life, for example, [6–9]. NO is produced by activation of nitric oxide synthase (NOS), which converts L-arginine to L-citrulline and NO [10]. The marker for NOS-positive neurons is nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) [11]. "
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    ABSTRACT: The aim of the study is to investigate the influence of prenatal temperature stimulation on neuronal NO synthase (nNOS) expression in the anterior hypothalamus of Muscovy duck embryos. Experiments were performed on embryonic day (E) E20, E23, E28, and E33 using histochemistry for identification of the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) as marker of NOS-containing neurons. Until the experiments, all duck embryos were incubated under standard temperature conditions (37.5°C). During 3 hours before the start of the experiments, one group was incubated at 37.5°C (control group), the second was warm-experienced at 39°C, and the third was cold-experienced at 34°C. In normal and warm-incubated duck embryos, nNOS activity could be first detected on E23. Particularly, after cold stimulation, a significant increase in nNOS activity was found in all embryos investigated even on day 20. Warm stimulation obviously induces the opposite effect, but at later embryonic age (E33). It can be concluded that probably in late-term bird embryos NO acts as a mediator of the neuronal cold pathway in the anterior hypothalamus, which might be improved by prenatal cold stimulation.
    The Scientific World Journal 04/2012; 2012(5):416936. DOI:10.1100/2012/416936 · 1.73 Impact Factor
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