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Nitric Oxide Actions in the Nervous System

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Neurodegenerative Diseases

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Abstract

Nitric oxide (NO) for many decades has been known to be a toxic gas, a constituent of air pollution, a component of cigarette smoke, and a by product of microbial metabolism. Only very recently has it been identified as a product of mammalian cells. The unique, although surprising, role for NO as a biological messenger molecule was developed by investigations in the fields of immunology, cardiovascular pharmacology, toxicology, and neurobiology (Dawson and Snyder 1994; Moncada and Higgs, 1993; Nathan, 1992; Feldman et al., 1993). In the nervous system the discovery of NO as a messenger molecule is changing the conventional concepts of how cells in the nervous system communicate. Classical neurotransmitters are enzymatically synthesized, stored in synaptic vesicles, and released by exocytosis from synaptic vesicles during membrane depolarization. These neurotransmitters mediate their biological actions by binding to membrane-associated receptors, which initiates intracellular changes in the postsynaptic cell. The activity of conventional neurotransmitters is terminated by either reuptake mechanisms or enzymatic degradation. There are multiple points at which biological control can be exherted over the production and activity of conventional neurotransmitters. None of these classical biological mechanisms are exploited by the nervous system to regulate the activity of NO. Instead, NO is synthesized on demand by the enzyme NO synthase (NOS) from the essential amino acid, L-arginine. NO is small, diffusible, membrane permeable and reactive. These chemical properties of NO make it a unique neuronal messenger molecule (Feldman et al., 1993). Since the cell can not sequester and regulate the local concentration of NO, the key to regulating NO activity is to control NO synthesis. Putative cellular targets of NO are rapidly being discovered as well as potential physiologic and pathophysiologic roles in the nervous system. NO may regulate neurotransmitter release, it may play a key role in morphogenesis and synaptic plasticity, it may regulate gene expression, and it may mediate inhibitory processes associated with sexual and aggressive behavior. Under conditions of excessive formation, NO is emerging as an important mediator of neurotoxicity in a variety of disorders of the nervous system.

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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, Maryland, 21287, USA

    Valina L. Dawson & Ted M. Dawson

  2. Department of Physiology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, Maryland, 21287, USA

    Valina L. Dawson

  3. Department of Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, Maryland, 21287, USA

    Valina L. Dawson & Ted M. Dawson

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  1. Valina L. Dawson
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  1. The George Washington University Medical Center, Washington, D.C., USA

    Gary Fiskum

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Dawson, V.L., Dawson, T.M. (1996). Nitric Oxide Actions in the Nervous System. In: Fiskum, G. (eds) Neurodegenerative Diseases. GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0209-2_31

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