Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Nov 15;100(10):2424–2429. doi: 10.1172/JCI119783

Nitric oxide in excitable tissues: physiological roles and disease.

K S Christopherson 1, D S Bredt 1
PMCID: PMC508441  PMID: 9366555

Full Text

The Full Text of this article is available as a PDF (186.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson D. C., Wildemann B., Sasaki M., Glass J. D., McArthur J. C., Christov V. I., Dawson T. M., Dawson V. L. Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science. 1996 Dec 13;274(5294):1917–1921. doi: 10.1126/science.274.5294.1917. [DOI] [PubMed] [Google Scholar]
  2. Beckman J. S., Koppenol W. H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996 Nov;271(5 Pt 1):C1424–C1437. doi: 10.1152/ajpcell.1996.271.5.C1424. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Hwang P. M., Glatt C. E., Lowenstein C., Reed R. R., Snyder S. H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. doi: 10.1038/351714a0. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030–9033. doi: 10.1073/pnas.86.22.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brenman J. E., Chao D. S., Gee S. H., McGee A. W., Craven S. E., Santillano D. R., Wu Z., Huang F., Xia H., Peters M. F. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996 Mar 8;84(5):757–767. doi: 10.1016/s0092-8674(00)81053-3. [DOI] [PubMed] [Google Scholar]
  8. Brenman J. E., Chao D. S., Xia H., Aldape K., Bredt D. S. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell. 1995 Sep 8;82(5):743–752. doi: 10.1016/0092-8674(95)90471-9. [DOI] [PubMed] [Google Scholar]
  9. Brown R. H. Free radicals, programmed cell death and muscular dystrophy. Curr Opin Neurol. 1995 Oct;8(5):373–378. doi: 10.1097/00019052-199510000-00009. [DOI] [PubMed] [Google Scholar]
  10. Burnett A. L., Nelson R. J., Calvin D. C., Liu J. X., Demas G. E., Klein S. L., Kriegsfeld L. J., Dawson V. L., Dawson T. M., Snyder S. H. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase. Mol Med. 1996 May;2(3):288–296. [PMC free article] [PubMed] [Google Scholar]
  11. Burnett A. L., Tillman S. L., Chang T. S., Epstein J. I., Lowenstein C. J., Bredt D. S., Snyder S. H., Walsh P. C. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol. 1993 Jul;150(1):73–76. doi: 10.1016/s0022-5347(17)35401-0. [DOI] [PubMed] [Google Scholar]
  12. Bö L., Dawson T. M., Wesselingh S., Mörk S., Choi S., Kong P. A., Hanley D., Trapp B. D. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol. 1994 Nov;36(5):778–786. doi: 10.1002/ana.410360515. [DOI] [PubMed] [Google Scholar]
  13. Campbell K. P. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell. 1995 Mar 10;80(5):675–679. doi: 10.1016/0092-8674(95)90344-5. [DOI] [PubMed] [Google Scholar]
  14. Carrier S., Nagaraju P., Morgan D. M., Baba K., Nunes L., Lue T. F. Age decreases nitric oxide synthase-containing nerve fibers in the rat penis. J Urol. 1997 Mar;157(3):1088–1092. [PubMed] [Google Scholar]
  15. Chao D. S., Gorospe J. R., Brenman J. E., Rafael J. A., Peters M. F., Froehner S. C., Hoffman E. P., Chamberlain J. S., Bredt D. S. Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy. J Exp Med. 1996 Aug 1;184(2):609–618. doi: 10.1084/jem.184.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Chung E., Curtis D., Chen G., Marsden P. A., Twells R., Xu W., Gardiner M. Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis. Am J Hum Genet. 1996 Feb;58(2):363–370. [PMC free article] [PubMed] [Google Scholar]
  17. Crosby G., Marota J. J., Huang P. L. Intact nociception-induced neuroplasticity in transgenic mice deficient in neuronal nitric oxide synthase. Neuroscience. 1995 Dec;69(4):1013–1017. doi: 10.1016/0306-4522(95)00395-y. [DOI] [PubMed] [Google Scholar]
  18. Daniel E. E., Haugh C., Woskowska Z., Cipris S., Jury J., Fox-Threlkeld J. E. Role of nitric oxide-related inhibition in intestinal function: relation to vasoactive intestinal polypeptide. Am J Physiol. 1994 Jan;266(1 Pt 1):G31–G39. doi: 10.1152/ajpgi.1994.266.1.G31. [DOI] [PubMed] [Google Scholar]
  19. Davies S. W., Turmaine M., Cozens B. A., DiFiglia M., Sharp A. H., Ross C. A., Scherzinger E., Wanker E. E., Mangiarini L., Bates G. P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 1997 Aug 8;90(3):537–548. doi: 10.1016/s0092-8674(00)80513-9. [DOI] [PubMed] [Google Scholar]
  20. Dawson V. L., Dawson T. M., London E. D., Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368–6371. doi: 10.1073/pnas.88.14.6368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dawson V. L., Kizushi V. M., Huang P. L., Snyder S. H., Dawson T. M. Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice. J Neurosci. 1996 Apr 15;16(8):2479–2487. doi: 10.1523/JNEUROSCI.16-08-02479.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Galpern W. R., Matthews R. T., Beal M. F., Isacson O. NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington's disease. Neuroreport. 1996 Nov 4;7(15-17):2639–2642. doi: 10.1097/00001756-199611040-00046. [DOI] [PubMed] [Google Scholar]
  23. Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [DOI] [PubMed] [Google Scholar]
  24. Hantraye P., Brouillet E., Ferrante R., Palfi S., Dolan R., Matthews R. T., Beal M. F. Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat Med. 1996 Sep;2(9):1017–1021. doi: 10.1038/nm0996-1017. [DOI] [PubMed] [Google Scholar]
  25. Hawkins R. D. NO honey, I don't remember. Neuron. 1996 Mar;16(3):465–467. doi: 10.1016/s0896-6273(00)80064-1. [DOI] [PubMed] [Google Scholar]
  26. Huang P. L., Dawson T. M., Bredt D. S., Snyder S. H., Fishman M. C. Targeted disruption of the neuronal nitric oxide synthase gene. Cell. 1993 Dec 31;75(7):1273–1286. doi: 10.1016/0092-8674(93)90615-w. [DOI] [PubMed] [Google Scholar]
  27. Huang Z., Huang P. L., Ma J., Meng W., Ayata C., Fishman M. C., Moskowitz M. A. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab. 1996 Sep;16(5):981–987. doi: 10.1097/00004647-199609000-00023. [DOI] [PubMed] [Google Scholar]
  28. Huang Z., Huang P. L., Panahian N., Dalkara T., Fishman M. C., Moskowitz M. A. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science. 1994 Sep 23;265(5180):1883–1885. doi: 10.1126/science.7522345. [DOI] [PubMed] [Google Scholar]
  29. Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci. 1997 Mar;20(3):132–139. doi: 10.1016/s0166-2236(96)10074-6. [DOI] [PubMed] [Google Scholar]
  30. Iadecola C., Zhang F., Xu X. Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum. Am J Physiol. 1993 Apr;264(4 Pt 2):R738–R746. doi: 10.1152/ajpregu.1993.264.4.R738. [DOI] [PubMed] [Google Scholar]
  31. 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 May 17;549(1):174–177. doi: 10.1016/0006-8993(91)90618-6. [DOI] [PubMed] [Google Scholar]
  32. Irikura K., Huang P. L., Ma J., Lee W. S., Dalkara T., Fishman M. C., Dawson T. M., Snyder S. H., Moskowitz M. A. Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6823–6827. doi: 10.1073/pnas.92.15.6823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kendrick K. M., Guevara-Guzman R., Zorrilla J., Hinton M. R., Broad K. D., Mimmack M., Ohkura S. Formation of olfactory memories mediated by nitric oxide. Nature. 1997 Aug 14;388(6643):670–674. doi: 10.1038/41765. [DOI] [PubMed] [Google Scholar]
  34. Kinouchi H., Epstein C. J., Mizui T., Carlson E., Chen S. F., Chan P. H. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11158–11162. doi: 10.1073/pnas.88.24.11158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Knowles R. G., Palacios M., Palmer R. M., Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5159–5162. doi: 10.1073/pnas.86.13.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kobzik L., Reid M. B., Bredt D. S., Stamler J. S. Nitric oxide in skeletal muscle. Nature. 1994 Dec 8;372(6506):546–548. doi: 10.1038/372546a0. [DOI] [PubMed] [Google Scholar]
  37. Kornau H. C., Seeburg P. H., Kennedy M. B. Interaction of ion channels and receptors with PDZ domain proteins. Curr Opin Neurobiol. 1997 Jun;7(3):368–373. doi: 10.1016/s0959-4388(97)80064-5. [DOI] [PubMed] [Google Scholar]
  38. Lee K. H., Baek M. Y., Moon K. Y., Song W. K., Chung C. H., Ha D. B., Kang M. S. Nitric oxide as a messenger molecule for myoblast fusion. J Biol Chem. 1994 May 20;269(20):14371–14374. [PubMed] [Google Scholar]
  39. Meller S. T., Gebhart G. F. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain. 1993 Feb;52(2):127–136. doi: 10.1016/0304-3959(93)90124-8. [DOI] [PubMed] [Google Scholar]
  40. Nakane M., Schmidt H. H., Pollock J. S., Förstermann U., Murad F. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 1993 Jan 25;316(2):175–180. doi: 10.1016/0014-5793(93)81210-q. [DOI] [PubMed] [Google Scholar]
  41. Penson D. F., Ng C., Cai L., Rajfer J., González-Cadavid N. F. Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod. 1996 Sep;55(3):567–574. doi: 10.1095/biolreprod55.3.567. [DOI] [PubMed] [Google Scholar]
  42. Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997 Jun 27;276(5321):2045–2047. doi: 10.1126/science.276.5321.2045. [DOI] [PubMed] [Google Scholar]
  43. Przedborski S., Jackson-Lewis V., Yokoyama R., Shibata T., Dawson V. L., Dawson T. M. Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4565–4571. doi: 10.1073/pnas.93.10.4565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rajfer J., Aronson W. J., Bush P. A., Dorey F. J., Ignarro L. J. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 1992 Jan 9;326(2):90–94. doi: 10.1056/NEJM199201093260203. [DOI] [PubMed] [Google Scholar]
  45. Roberts C. K., Barnard R. J., Scheck S. H., Balon T. W. Exercise-stimulated glucose transport in skeletal muscle is nitric oxide dependent. Am J Physiol. 1997 Jul;273(1 Pt 1):E220–E225. doi: 10.1152/ajpendo.1997.273.1.E220. [DOI] [PubMed] [Google Scholar]
  46. Samdani A. F., Dawson T. M., Dawson V. L. Nitric oxide synthase in models of focal ischemia. Stroke. 1997 Jun;28(6):1283–1288. doi: 10.1161/01.str.28.6.1283. [DOI] [PubMed] [Google Scholar]
  47. Scharton-Kersten T. M., Yap G., Magram J., Sher A. Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii. J Exp Med. 1997 Apr 7;185(7):1261–1273. doi: 10.1084/jem.185.7.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Schuman E. M., Madison D. V. Nitric oxide and synaptic function. Annu Rev Neurosci. 1994;17:153–183. doi: 10.1146/annurev.ne.17.030194.001101. [DOI] [PubMed] [Google Scholar]
  49. Sheng M. PDZs and receptor/channel clustering: rounding up the latest suspects. Neuron. 1996 Oct;17(4):575–578. doi: 10.1016/s0896-6273(00)80190-7. [DOI] [PubMed] [Google Scholar]
  50. Shibuki K., Okada D. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature. 1991 Jan 24;349(6307):326–328. doi: 10.1038/349326a0. [DOI] [PubMed] [Google Scholar]
  51. Silvagno F., Xia H., Bredt D. S. Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle. J Biol Chem. 1996 May 10;271(19):11204–11208. doi: 10.1074/jbc.271.19.11204. [DOI] [PubMed] [Google Scholar]
  52. Son H., Hawkins R. D., Martin K., Kiebler M., Huang P. L., Fishman M. C., Kandel E. R. Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell. 1996 Dec 13;87(6):1015–1023. doi: 10.1016/s0092-8674(00)81796-1. [DOI] [PubMed] [Google Scholar]
  53. Stamler J. S. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994 Sep 23;78(6):931–936. doi: 10.1016/0092-8674(94)90269-0. [DOI] [PubMed] [Google Scholar]
  54. Vernet D., Cai L., Garban H., Babbitt M. L., Murray F. T., Rajfer J., Gonzalez-Cadavid N. F. Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and BBZ/WORdp (type II) rats with erectile dysfunction. Endocrinology. 1995 Dec;136(12):5709–5717. doi: 10.1210/endo.136.12.7588327. [DOI] [PubMed] [Google Scholar]
  55. Wang T., Xie Z., Lu B. Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses. Nature. 1995 Mar 16;374(6519):262–266. doi: 10.1038/374262a0. [DOI] [PubMed] [Google Scholar]
  56. Welch K. M. Drug therapy of migraine. N Engl J Med. 1993 Nov 11;329(20):1476–1483. doi: 10.1056/NEJM199311113292008. [DOI] [PubMed] [Google Scholar]
  57. Wiesenfeld-Hallin Z., Hao J. X., Xu X. J., Hökfelt T. Nitric oxide mediates ongoing discharges in dorsal root ganglion cells after peripheral nerve injury. J Neurophysiol. 1993 Dec;70(6):2350–2353. doi: 10.1152/jn.1993.70.6.2350. [DOI] [PubMed] [Google Scholar]
  58. Wu H. H., Williams C. V., McLoon S. C. Involvement of nitric oxide in the elimination of a transient retinotectal projection in development. Science. 1994 Sep 9;265(5178):1593–1596. doi: 10.1126/science.7521541. [DOI] [PubMed] [Google Scholar]
  59. Wu W., Li L. Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neurosci Lett. 1993 Apr 30;153(2):121–124. doi: 10.1016/0304-3940(93)90303-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES