Nitric Oxide Actions in the Nervous System

  • Valina L. Dawson
  • Ted M. Dawson
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

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.

Keywords

Nitric Oxide Nitric Oxide NMDA Receptor Glutamate Neurotoxicity NADPH Diaphorase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abu-Soud HM and Stuehr DJ. Nitric oxide synthases reveal a role for calmodulin in controlling electron transfer. Proc. Natl. Acad. Sci. USA 1993; 90: 10769–10772.PubMedCrossRefGoogle Scholar
  2. Baek KJ, Thiel BA, Lucas S, and Stuehr DJ. Macrophage nitric oxide subunits. Purification, characterization, and the role of prosthetic groups and substrate in regulating their association into a dimeric enzyme. J. Biol. Chem. 1993; 268: 21120–21129.PubMedGoogle Scholar
  3. Beckman JS, Ischiropoulos H, Zhu L, van der Woerd M, Smith C, Chen J, Harrison J, Martin JC, and Tsai M. Kinetics of Superoxide dismutase-and iron catalyzed nitration of phenolics by peroxynitrite. Arch. Biochem. Biophys. 1992; 298: 438–445.PubMedCrossRefGoogle Scholar
  4. Bo L, Dawson TM, Wesselingh S, et al. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann. Neurol. 1994; in press.Google Scholar
  5. Bohme GA, Bon C, Stutzmann J-M, Doble A, Blanchard J-C. Possible involvment of nitric oxide in long-term potentiation. Eur.J. Pharm. 1991; 199: 379–381.CrossRefGoogle Scholar
  6. Bredt DS, Ferris CD, Snyder SH. Nitric oxide synthase regulatory sites. J. Biol. Chem. 1992; 267:10976–10981.PubMedGoogle Scholar
  7. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron. 1991; 7:615–624.PubMedCrossRefGoogle Scholar
  8. Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990; 347:768–770.PubMedCrossRefGoogle Scholar
  9. Bredt DS, Snyder SH. Nitric oxide, a physiological messenger molecule. Annu. Rev. Biochem. 1994;63:in press.Google Scholar
  10. Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. U.S.A. 1990; 87:682–685.PubMedCrossRefGoogle Scholar
  11. Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990; 345:346–347.PubMedCrossRefGoogle Scholar
  12. Burnett AL, Lowenstein CJ, Bredt DS, Chang TSK, Snyder SH. Nitric Oxide: a physiologic mediator of penile erection. Science 1992; 257:401–403.PubMedCrossRefGoogle Scholar
  13. Carreau A, Duval D, Poignet H, Scatton B, Vige X, Nowicki J-P. Neuroprotective efficacy of Nw-nitro-L-arginine after focal cerebral ischemia in the mouse and inhibition of cortical nitric oxide synthase. Eur. J. Pharmacol. 1994; 256:241–249.PubMedCrossRefGoogle Scholar
  14. Castro L, Rodriguez M, and Radi R. Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J. Biol. Chem. 1994; 269: 29409–29415.PubMedGoogle Scholar
  15. Chao CC, Hu S, Molitor TW, Shaskan EG and Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol 1992; 149: 2736–2741.PubMedGoogle Scholar
  16. Cho HJ, Xie QW, Calaycay J, Mumford RA, Swiderek KM, Lee TD, and Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. J. Exp. Med. 1992; 176: 599–604.PubMedCrossRefGoogle Scholar
  17. Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988; 1:623–634.PubMedCrossRefGoogle Scholar
  18. Clancy RM, Levartovsky D, Leszczynska-Piziak J, Yegudin J, Abramson SB. Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary. Proc. Natl. Acad. Sci. U.S.A. 1994; 91:3680–3684.PubMedCrossRefGoogle Scholar
  19. Crow JP, Beekman JS and McCord JM. Sensitivity of the essential zinc-thiolate moiety of yeast alcohol dehydrogenase to hypochlorite and peroxynitrite. Biochem. 1995; 34: 3544–3552.CrossRefGoogle Scholar
  20. Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc. Natl. Acad. Sci. U.S.A. 1991; 88:7797–7801.PubMedCrossRefGoogle Scholar
  21. Dawson TM, Dawson VL, Snyder SH. A novel neuronal messenger molecule in brain: the free radical, nitric oxide. Ann. Neurol. 1992;32:297–311.PubMedCrossRefGoogle Scholar
  22. Dawson TM, Hung K, Dawson VL, Steiner JP, Snyder SH. Neuroprotective effects of gangliosides may involve inhibition of nitric oxide synthase. Ann. Neurol. 1995; 37: 115–118.PubMedCrossRefGoogle Scholar
  23. Dawson TM, Snyder SH. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J.Neurosci. 1994; 14: 5147–5159.PubMedGoogle Scholar
  24. Dawson TM, Steiner JP, Dawson VL, Dinerman JL, Uhl GR, Snyder SH. Immunosuppressant, FK506, enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity. Proc. Natl. Acad. Sci. U.S.A. 1993; 90:9808–9812.PubMedCrossRefGoogle Scholar
  25. Dawson V, Brahmbhatt HP, Mong JA, Dawson TM Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. Neuropharmacol. 1995; 33:1425–1430.CrossRefGoogle Scholar
  26. Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder SH. Mechanisms of nitric oxide mediated neurotoxicity in primary brain cultures. J. Neurosci. 1993; 13:2651–2661.PubMedGoogle Scholar
  27. Dawson VL, Dawson TM, Uhl GR, Snyder SH. Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc. Natl. Acad. Sci. U.S.A. 1993; 90:3256–3259.PubMedCrossRefGoogle Scholar
  28. Desai KM, Sessa WC and Vane JR. Involvement of nitric oxide in the reflex relaxation of the stomach to accomodate food or fluid. Nature 1991; 351: 477–479.PubMedCrossRefGoogle Scholar
  29. Dinerman JL, Dawson TM, Schell MJ, Snowman A, Snyder SH. Endothelial nitric oxide synthase localized to hippocampal pyramidal cells: implications for synaptic plasticity. Proc. Natl. Acad. Sci. U.S.A. 1994; 91:4214–4218.PubMedCrossRefGoogle Scholar
  30. Dinerman JL, Steiner JP, Dawson TM, Dawson VL, and Snyder SH. Protein phosphorylation inhibits neuronal nitric oxide synthase. Neuropharmacology. 1994; 33: 1245-1252.Google Scholar
  31. Ding AH, Nathan CF and Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. J. Immunol. 1988; 141: 2407.Google Scholar
  32. Drapier J-C, Hirling H, Wietzerbin J, Kaldy P, Kuhn LC. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBOJ. 1993; 12:3643–3649.Google Scholar
  33. Faraci FM. Regulation of the cerebral circulation by endothelium. Pharmac. Ther. 1992; 56:1–22.CrossRefGoogle Scholar
  34. Feldman PL, Griffith OW, Stuehr DJ. The surprising life of nitric oxide. Chemical & Engineering News. 1993;12:26–38.Google Scholar
  35. Galea E, Feinstein and Reis DJ. Induction of calcium-dependent nitric oxide synthase activity in primary rat glial cultures. Proc. Natl. Acad. Sci. USA 1992; 89:10945–10949.PubMedCrossRefGoogle Scholar
  36. Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988; 336:385–388.PubMedCrossRefGoogle Scholar
  37. Green LC, Ruiz-de-Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannenbaum SR. Nitrate biosynthesis in man. Proc Natl. Acad. Sci. USA 1981a; 78:7764–7768.PubMedCrossRefGoogle Scholar
  38. Green LC, Tannenbaum SR, Goldman P. Nitrate synthesis in the germfree and conventional rat. Science 1981b; 212:56–68.PubMedCrossRefGoogle Scholar
  39. Haley JE, Wilcox GL, Chapman PF. The role of nitric oxide in hippocampal long-term potentiation. Neuron 1992; 8: 211–216.PubMedCrossRefGoogle Scholar
  40. Hausladen A and Fridovich I. Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J. Biol. Chem. 1994; 269: 29405–29408.PubMedGoogle Scholar
  41. Henry Y, Lepoivre M, Drapier JC, Ducrocq C, Boucher JL, and Guissani A. EPR characterization of molecular targets for NO in mammalian cells and organelles. FASEB J 1993; 7: 1124–1134.PubMedGoogle Scholar
  42. Hess DT, Patterson SI, Smith DS, Pate Skene JH. Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide. Nature. 1993;366:562–565.PubMedCrossRefGoogle Scholar
  43. Hibbs JB Jr., Vavrin Z, Taintor RR. L-arginine is required for expression fo the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J. Immunol. 1987b: 138: 550–565.PubMedGoogle Scholar
  44. Hibbs JB Jr., Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deaminase and imino nitrogen oxidation to nitrite. Science 1987a; 235: 473–476.PubMedCrossRefGoogle Scholar
  45. Hirsch DB, Steiner JP, Dawson TM, Mammen A, Hayek E, Snyder SH. Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes. Cur. Biol. 1993; 3:749–754.CrossRefGoogle Scholar
  46. Hope BT, Michael GJ, Knigge KM, Vincent SR. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc. Natl. Acad. Sci. U.S.A. 1991; 88:2811–2814.PubMedCrossRefGoogle Scholar
  47. Huang PL, Dawson TM, Bredt DS, Snyder SH, Fishman MC. Targeted disruption of the neuronal nitric oxide synthase gene. Cell. 1993;75:1273–1286.PubMedCrossRefGoogle Scholar
  48. Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC and Moskowtiz MA. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 1994; 265:1883–1885.PubMedCrossRefGoogle Scholar
  49. Hyman BT, Marzloff K, Wenniger JJ, Dawson TM, Bredt DS, Snyder SH. Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer’s disease. Ann Neurol 1992; 32: 818–820.PubMedCrossRefGoogle Scholar
  50. ladecola C, Pelligrino DA, Moskowitz MA and Lassen NA. Nitric oxide synthase inhibition and cerebrovascular regulation. J. Cereb. Blood Flow and Metab. 1994; 14: 175–192.CrossRefGoogle Scholar
  51. Iadecola C. Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? Trends Neurosci 1993; 16:206–214.PubMedCrossRefGoogle Scholar
  52. Ignarro LJ and Gruetter CA. Requirement of thiols for activation of coronary arterial guanylate cyclase by glycerol trinitrate and sodium nitrite: possible involvment of s-nitrosothiols. Biochim. Biophys. Acta. 1980; 631:221–231.PubMedCrossRefGoogle Scholar
  53. Ignarro LJ, Lippton H, Edwards JC, Baricos WH, Hyman AL, Kadowitz PJ, Gruetter CA Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J. Pharmacol. Exp. Ther. 1981; 218:739–749.PubMedGoogle Scholar
  54. Ignarro LJ. Biosynthesis and metabolism of endothelium-derived relaxing factor. Annu. Rev. Pharmacol. Toxicol. 1990; 30: 535–560.PubMedCrossRefGoogle Scholar
  55. Inagaki S, Suzuki K, Taniguchi N, Takagi H. Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum. Brain. Res. 1991; 549:174–177.PubMedCrossRefGoogle Scholar
  56. Jaffrey SR, Cohen NA, Rouault TA, Klausner RD, Snyder SH. The iron-responsive element binding protein: a novel target for synaptic actions of nitric oxide. Proc. Natl. Acad. Sci, USA. 1994; 91: 12994–12998.PubMedCrossRefGoogle Scholar
  57. King PA, Adnerson VE, Edwards JO, Gustafson G, Plumb RC, and Suggs JW. A stable solid that generates hydroxyl radical upon dissolution in aqueous solution: Reaction with proteins and nucleic acids. J. Am. Chem. Soc. 1992; 114: 5430–5432.CrossRefGoogle Scholar
  58. Kinouchi H, Epstein CJ, Mizue T, et al. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn Superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 1991;88:11158–11162.PubMedCrossRefGoogle Scholar
  59. Koh J-Y and Choi DW. Vulnerability of cultured cortical neurons to damage by excitotoxins: differential susceptibility of neurons containing NADPH-diaphorase. J. Neurosci. 1988:8:2153–2163.PubMedGoogle Scholar
  60. Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beekman JS. Peroxynitrite, a cloaked osidant formed by nitric oxide and Superoxide. Chem. Res. Toxicol. 1992; 5: 834–842.PubMedCrossRefGoogle Scholar
  61. Lautier D, Lagueux J, Thibodeau J, Menard L, and Poirier GG. Molecular and biochemical features of poly(ADP-ribose) metabolism. Mol. Cell. Biochem. 1993; 122: 171–193.PubMedCrossRefGoogle Scholar
  62. Lipton SA, Choi YB, Pan Z-H, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993;364:626–632.PubMedCrossRefGoogle Scholar
  63. Lipton SA. Models of neuronal injury in AIDS: another role for the NMDA receptor? Trends Neurosci. 1992; 15:75–79.PubMedCrossRefGoogle Scholar
  64. Lustig HS, von Brauchitsch KL, Chan J, Greenberg DA. Ethanol and excitotoxicity in cultured cortical neurons: differential sensitivity of N-methyl-D-aspartate and sodium nitroprusside toxicity. J. Neurochem. 1992; 577: 343–346.Google Scholar
  65. Malinski T, Bailey F, Zhang ZG, Chopp M. Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J. Cereb. Blood. Flow. Metab. 1993; 13:355–358.PubMedCrossRefGoogle Scholar
  66. Marietta MA. Nitric oxide synthase structure and mechanism. J. Biol. Chem. 1993;268:12231–12234.Google Scholar
  67. Matsumoto T, Nakane M, Pollock JS, Kuk JE, Forstermann U. A correlation between soluble nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative. Neurosci. Letts. 1993;155:61–64.CrossRefGoogle Scholar
  68. McDonald LJ and Moss J. Stimulation by nitric oxide of an NAD linkage to glyceraldehyde-3-phosphate dehydrogenase. Proc. Natl. Acad. Sci. USA 1993; 90: 6238–6241.PubMedCrossRefGoogle Scholar
  69. Meldrum B, Garthwaite J. Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends. Pharmacol. Sci. 1990; 11:379–387.PubMedCrossRefGoogle Scholar
  70. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J. Immunol. 1993;151:2132–2141.PubMedGoogle Scholar
  71. Mollace V, Colasanti M, Persichini T, Bagetta G, Lauro GM, Nistico G. HIV gp120 glycoprotein stimulates the inducible isoform of NO synthase in human cultured astrocytoma cells. Biochem. Biophys. Res. Comm. 1993; 194:439–445.PubMedCrossRefGoogle Scholar
  72. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 1993;329:2002–2012.PubMedCrossRefGoogle Scholar
  73. Montague PR, Gancayco CD, Winn MJ, Marchase RB, Friedlander MJ. Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science. 1994;263:973–977.PubMedCrossRefGoogle Scholar
  74. Moreno JJ and Pryor QA. Inactivation of α-1-proteinase inhibitior by peroxynitrite. Chem. Res. Toxiocol. 1992; 5: 425–431.CrossRefGoogle Scholar
  75. Murphy S, Simmons ML, Agullo L, Garcia A, Feinstein DL, Galea E, Reis DJ, Minc-Golomb D, Schwartz JP. Synthesis of nitric oxide in CNS glial cells. Trends in Neurosci. 1993; 16:323–328.CrossRefGoogle Scholar
  76. Nathan C, Xie Q-W. Regulation of biosynthesis of nitric oxide. J. Biol. Chem. 1994;19:13725–13728.Google Scholar
  77. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6:3051–3064.PubMedGoogle Scholar
  78. Nozaki K, Moskowitz MA, Maynard KI, et al. Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibers in rat and human cerebral arteries. J. Cerebral. Blood. Flow, and Metabolism. 1993; 13:70–79.CrossRefGoogle Scholar
  79. O’Dell TJ, Hawkins RD, Kandel ER, Arancio O. Tests of the roles of two diffusable substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc. Natl. Acad. Sci. U.S.A. 1991; 88:11285–11289.PubMedCrossRefGoogle Scholar
  80. O’Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kandel ER and Fishman MC. Blockade of long-term potentiation by inhibitors of nitric oxide synthase in mice lacking the neuronal isoform suggests a role for the endothelial isoform. Science. 1994; 265: 542-546.Google Scholar
  81. Oury TD, Ho Y-S, Piantadosi CA, Crapo JD. Extracellular Superoxide dismutase, nitric oxide, and central nervous system O2 toxicity. Proc. Natl. Acad. Sci. U.S.A. 1992;89:9715–9719.PubMedCrossRefGoogle Scholar
  82. Radi R, Beekman JS, Bush KM, Freeman BA. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of Superoxide and nitric oxide. J. Biol. Chem. 1991; 266:4244–4250.PubMedGoogle Scholar
  83. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric oxide as a mediator of the corpus cavernosum in response to nonadrenergic noncholinergic transmission. New. Eng. J. Med. 1992; 326:90–94.PubMedCrossRefGoogle Scholar
  84. Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P. Nitric oxide activates cyclooxygenase enzymes. Proc. Natl. Acad. Sci. U.S.A. 1993; 90:7240–7244.PubMedCrossRefGoogle Scholar
  85. Sandberg K, Berry CJ, Eugster E, Rogers TB. A role for cGMP during tetanus toxin blockade of acetylcholine release in the rat pheochromocytoma (PC12) cell lines. J Neurosci 1989; 9:3946–3954.PubMedGoogle Scholar
  86. Schuman EM, Madison DV. Locally distributed synaptic potentiation in the hippocampus. Science. 1994;263:532–536.PubMedCrossRefGoogle Scholar
  87. Schuman EM, Madison DV. Nitric oxide and synaptic function. Annu. Rev. Neurosci. 1994;17:153–183.PubMedCrossRefGoogle Scholar
  88. Schuman EM, Madison DV. The intercellular messenger nitric oxide is required for longterm potentiation. Science 1991; 254:1503–1506.PubMedCrossRefGoogle Scholar
  89. Schumann EM and Madison DV. Nitric oxide and synpatic function. Ann. Rev. Neurosci. 1994; 17: 153–183.CrossRefGoogle Scholar
  90. Sharkey J, Butcher SP. Immunophillins mediate the neuroprotective effects of FK506 in focal cerebral ischemia. Nature 1994; 371:336–339.PubMedCrossRefGoogle Scholar
  91. Stamler JS, Simon DI, Osborne JA, et al. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc. Natl. Acad. Sci. U.S.A. 1992; 89:444–448.PubMedCrossRefGoogle Scholar
  92. Stamler JS, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, Singel DJ and Loscalzo J. S-nitrosylation of proteins with nitric oxide: synthesis and characterization ofbiolgocially active compounds. Proc. Natl. Acad. Sci. USA 1992:89:444–448.PubMedCrossRefGoogle Scholar
  93. Stamler JS. Redox signalling: Nitrosylation and related target interactions of nitric oxide. Cell 1994; 78: 931–936.PubMedCrossRefGoogle Scholar
  94. Stuehr DJ and Marietta MA. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc. Natl. Acad. Sci. USA 1985; 82: 7738–7742.PubMedCrossRefGoogle Scholar
  95. Stuehr DJ, and Nathan CF. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumore target cells. J. Exp. Med. 1989; 169: 1543–1555.PubMedCrossRefGoogle Scholar
  96. Thomas E, Pearse AGE. The solitary active cells. Histochemical demonstration of damage-resistant nerve cells with a TPN-diaphorase reaction. Acta. Neuropathol. 1964; 3:238–249.PubMedCrossRefGoogle Scholar
  97. Thomsen LL, Iversen HK, Brinck TA, Olesen J. Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers. Cephalalgia. 1993; 13:395–399.PubMedCrossRefGoogle Scholar
  98. Visser JJ, Scholten RJPM, Hoekman K. Nitric oxide synthesis in meningococcal meningitis. Ann. Int. Med. 1994; 120:345–346.PubMedGoogle Scholar
  99. Weiss G, Goossen B, Doppier W, Fuchs D, Pantopoulos K, Werner-Felmayer G, Wachter H, Hentze MW. Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. EMBO J. 1993;12:3651–3657.PubMedGoogle Scholar
  100. Wu W and Li L. Inhibition of nitric oxide synthase reduces motoneurons death due to spinal root avulsion. Neurosci. Lett. 1993; 153:121–124.PubMedCrossRefGoogle Scholar
  101. Wu W, Liuzzi FJ, Schinco FP, Depto AS, Li Y, Mong JA, Dawson TM, Snyder SH. Neuronal nitric oxide synthase is induced in spinal neurons by traumatic injury. Neurosci. 1994; 61: 719–726.CrossRefGoogle Scholar
  102. Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly (ADP-ribose) synthetase in neurotoxicity. Science 1994; 263:687–689.PubMedCrossRefGoogle Scholar
  103. Zorumski CF, Izumi Y. Nitric oxide and hippocampal synaptic plasticity. Biochem. Pharmacol. 1993; 46: 777–785.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Valina L. Dawson
    • 1
    • 2
    • 3
  • Ted M. Dawson
    • 1
    • 3
  1. 1.Department of NeurologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of PhysiologyJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA

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