Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Localization of nitric oxide synthase indicating a neural role for nitric oxide

Abstract

NITRIC oxide (NO), apparently identical to endothelium-derived relaxing factor in blood vessels1–3, is also formed by cytotoxic macrophages4,5, in adrenal gland6 and in brain tissue7–9, where it mediates the stimulation by glutamate of cyclic GMP formation in the cerebellum10,11. Stimulation of intestinal12 or anococcygeal13–15 nerves liberates NO, and the resultant muscle relaxation is blocked by arginine derivatives that inhibit NO synthesis. It is, however, unclear whether in brain or intestine, NO released following nerve stimulation is formed in neurons, glia, fibroblasts, muscle or blood cells, all of which occur in proximity to neurons and so could account for effects of nerve stimulation on cGMP and muscle tone. We have now localized NO synthase protein immunohisto-chemically in the rat using antisera to the purified enzyme16. We demonstrate NO synthase in the brain to be exclusively associated with discrete neuronal populations. NO synthase is also concentrated in the neural innervation of the posterior pituitary, in autonomic nerve fibres in the retina, in cell bodies and nerve fibres in the myenteric plexus of the intestine, in adrenal medulla, and in vascular endothelial cells. These prominent neural localizations provide the first conclusive evidence for a strong association of NO with neurons.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Moncada, S., Radomski, M. W. & Palmer, R. M. J. Biochem. Pharm. 37, 2495–2501 (1988).

    Article  CAS  Google Scholar 

  2. Furchgott, R. F. & Vanhoutte, P. M. FASEB J. 3, 2007–2018 (1988).

    Article  Google Scholar 

  3. Ignarro, L. J. FASEB J. 3, 31–36 (1989).

    Article  CAS  Google Scholar 

  4. Hibbs, J. B., Jr., Vavrin, Z. & Taintor, R. R. J. Immun. 138, 550–565 (1987).

    CAS  PubMed  Google Scholar 

  5. Marletta, M. A., Yoon, P. S., Iyengar, R., Leaf, C. D. & Wishrock, J. S. Biochemistry 27, 8706–8711 (1988).

    Article  CAS  Google Scholar 

  6. Palacios, M., Knowles, R. G., Palmer, R. M. J. & Moncada, S. Biochem. biophys. Res. Commun. 165, 802–809 (1989).

    Article  CAS  Google Scholar 

  7. Garthwaite, J., Charles, S. J. & Chess-Williams, R. Nature 336, 385–388 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Knowles, R. G., Palacios, M., Palmer, R. M. J. & Moncada, S. Proc. natn. Acad. Sci. U.S.A. 86, 5159–5162 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Schmidt, H. H. H. W., Wilke, P., Evers, B. & Bohme, E. Biochem. biophys. Res. Commun 165, 284–291 (1989).

    Article  CAS  Google Scholar 

  10. Brect, D. S. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 86, 9030–9033 (1989).

    Article  ADS  Google Scholar 

  11. Garthwaite, J., Garthwaite, G., Palmer, R. M. J. & Moncada, S. Eur. J. Pharmacol. 172, 413–416 (1989).

    Article  CAS  Google Scholar 

  12. Bult, H. et al. Nature 345, 346–347 (1990).

    Article  ADS  CAS  Google Scholar 

  13. Gillespie, J. S., Liu, X. & Martin, W. Br. J. Pharmac. 98, 1080–1082 (1989).

    Article  CAS  Google Scholar 

  14. Ramagopal, M. W. & Leighton, H. J. Eur. J. Pharmac. 174, 297–299 (1989).

    Article  CAS  Google Scholar 

  15. Gibson, A., Mirzazadeh, S., Hobbs, A. J. & Moore, P. K. Br. J. Pharmac. 99, 602–606 (1990).

    Article  CAS  Google Scholar 

  16. Bredt, D. S. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 87, 682–685 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Ross, C. A. et al. Nature 339, 468–470 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Palmer, R. M. J. & Moncada, S. Biochem. biophys. Res. Commun. 158, 348–352 (1989).

    Article  CAS  Google Scholar 

  19. Mayer, B., Schmidt, K., Humbert, P. & Bohme, E. Biochem. biophys. Res. Commun. 164, 678–685 (1989).

    Article  CAS  Google Scholar 

  20. Tayeh, M. A. & Marletta, M. A. J. biol. Chem. 264, 19654–19658 (1989).

    CAS  PubMed  Google Scholar 

  21. Kwon, N. S., Nathan, C. F. & Stuehr, D. J. J. biol. Chem. 264, 20496–20501 (1989).

    CAS  PubMed  Google Scholar 

  22. Ferrendelli, J. A. Adv. Cyclic Nucleotide Res. 9, 453–464 (1978).

    CAS  PubMed  Google Scholar 

  23. Marjorie, A. A., Lewicki, J. A., Brandwein, H. J. & Murad, F. Proc. natn. Acad. Sci. U.S.A. 79, 1316–1320 (1982).

    Article  ADS  Google Scholar 

  24. Zwiller, J., Ghandour, M. S., Revel, M. O. & Basset, P. Neurosci. Lett. 23, 31–36 (1981).

    CAS  PubMed  Google Scholar 

  25. Novelli, A., Nicoletti, F., Wroblewski, J. T., Alho, H. & Costa, E. J. Neurosci. 7, 40–47 (1987).

    Article  CAS  Google Scholar 

  26. Dohi, T., Morita, K. & Tsujimoto, A. Eur. J. Pharmaco. 94, 331–335 (1983).

    Article  CAS  Google Scholar 

  27. O'Sullivan, A. J. & Burgoyne, R. D. J. Neurochem. 54, 1805–1808 (1990).

    Article  CAS  Google Scholar 

  28. Toda, N. & Okamura, T. Jap. J. Pharm. 52, 170–173 (1990).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bredt, D., Hwang, P. & Snyder, S. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347, 768–770 (1990). https://doi.org/10.1038/347768a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/347768a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing