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. 1994 Mar 15;91(6):2151–2155. doi: 10.1073/pnas.91.6.2151

Existence of nitric oxide synthase in rat hippocampal pyramidal cells.

B Wendland 1, F E Schweizer 1, T A Ryan 1, M Nakane 1, F Murad 1, R H Scheller 1, R W Tsien 1
PMCID: PMC43328  PMID: 7510887

Abstract

It has been proposed that nitric oxide (NO) serves as a key retrograde messenger during long-term potentiation at hippocampal synapses, linking induction of long-term potentiation in postsynaptic CA1 pyramidal cells to expression of long-term potentiation in presynaptic nerve terminals. However, nitric oxide synthase (NOS), the proposed NO-generating enzyme, has not yet been detected in the appropriate postsynaptic cells. We here demonstrate specific NOS immunoreactivity in the CA1 region of hippocampal sections by using an antibody specific for NOS type I and relatively gentle methods of fixation. NOS immunoreactivity was found in dendrites and cell bodies of CA1 pyramidal neurons. Cultured hippocampal pyramidal cells also displayed specific immunostaining. Control experiments showed no staining with preimmune serum or immune serum that was blocked with purified NOS. These results demonstrate that CA1 pyramidal cells contain NOS, as required were NO involved in retrograde signaling during hippocampal synaptic plasticity.

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Selected References

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

  1. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  2. Bredt D. S., Glatt C. E., Hwang P. M., Fotuhi M., Dawson T. M., Snyder S. H. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron. 1991 Oct;7(4):615–624. doi: 10.1016/0896-6273(91)90374-9. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Snyder S. H. Nitric oxide, a novel neuronal messenger. Neuron. 1992 Jan;8(1):3–11. doi: 10.1016/0896-6273(92)90104-l. [DOI] [PubMed] [Google Scholar]
  4. Böhme G. A., Bon C., Stutzmann J. M., Doble A., Blanchard J. C. Possible involvement of nitric oxide in long-term potentiation. Eur J Pharmacol. 1991 Jul 9;199(3):379–381. doi: 10.1016/0014-2999(91)90505-k. [DOI] [PubMed] [Google Scholar]
  5. Culotta E., Koshland D. E., Jr NO news is good news. Science. 1992 Dec 18;258(5090):1862–1865. doi: 10.1126/science.1361684. [DOI] [PubMed] [Google Scholar]
  6. Dani J. W., Chernjavsky A., Smith S. J. Neuronal activity triggers calcium waves in hippocampal astrocyte networks. Neuron. 1992 Mar;8(3):429–440. doi: 10.1016/0896-6273(92)90271-e. [DOI] [PubMed] [Google Scholar]
  7. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  8. Förstermann U., Schmidt H. H., Pollock J. S., Sheng H., Mitchell J. A., Warner T. D., Nakane M., Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol. 1991 Oct 24;42(10):1849–1857. doi: 10.1016/0006-2952(91)90581-o. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991 Feb;14(2):60–67. doi: 10.1016/0166-2236(91)90022-m. [DOI] [PubMed] [Google Scholar]
  11. Haley J. E., Wilcox G. L., Chapman P. F. The role of nitric oxide in hippocampal long-term potentiation. Neuron. 1992 Feb;8(2):211–216. doi: 10.1016/0896-6273(92)90288-o. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Malgaroli A., Tsien R. W. Glutamate-induced long-term potentiation of the frequency of miniature synaptic currents in cultured hippocampal neurons. Nature. 1992 May 14;357(6374):134–139. doi: 10.1038/357134a0. [DOI] [PubMed] [Google Scholar]
  14. Matus A. Microtubule-associated proteins: their potential role in determining neuronal morphology. Annu Rev Neurosci. 1988;11:29–44. doi: 10.1146/annurev.ne.11.030188.000333. [DOI] [PubMed] [Google Scholar]
  15. Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
  16. Murphy S., Simmons M. L., Agullo L., Garcia A., Feinstein D. L., Galea E., Reis D. J., Minc-Golomb D., Schwartz J. P. Synthesis of nitric oxide in CNS glial cells. Trends Neurosci. 1993 Aug;16(8):323–328. doi: 10.1016/0166-2236(93)90109-y. [DOI] [PubMed] [Google Scholar]
  17. O'Dell T. J., Hawkins R. D., Kandel E. R., Arancio O. Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11285–11289. doi: 10.1073/pnas.88.24.11285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pollock J. S., Förstermann U., Mitchell J. A., Warner T. D., Schmidt H. H., Nakane M., Murad F. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10480–10484. doi: 10.1073/pnas.88.23.10480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schmidt H. H., Gagne G. D., Nakane M., Pollock J. S., Miller M. F., Murad F. Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem. 1992 Oct;40(10):1439–1456. doi: 10.1177/40.10.1382087. [DOI] [PubMed] [Google Scholar]
  20. Schuman E. M., Madison D. V. A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science. 1991 Dec 6;254(5037):1503–1506. doi: 10.1126/science.1720572. [DOI] [PubMed] [Google Scholar]
  21. Southam E., Garthwaite J. The nitric oxide-cyclic GMP signalling pathway in rat brain. Neuropharmacology. 1993 Nov;32(11):1267–1277. doi: 10.1016/0028-3908(93)90021-t. [DOI] [PubMed] [Google Scholar]
  22. Valtschanoff J. G., Weinberg R. J., Kharazia V. N., Nakane M., Schmidt H. H. Neurons in rat hippocampus that synthesize nitric oxide. J Comp Neurol. 1993 May 1;331(1):111–121. doi: 10.1002/cne.903310107. [DOI] [PubMed] [Google Scholar]
  23. Vincent S. R., Kimura H. Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience. 1992;46(4):755–784. doi: 10.1016/0306-4522(92)90184-4. [DOI] [PubMed] [Google Scholar]
  24. Wallace M. N., Fredens K. Activated astrocytes of the mouse hippocampus contain high levels of NADPH-diaphorase. Neuroreport. 1992 Nov;3(11):953–956. doi: 10.1097/00001756-199211000-00001. [DOI] [PubMed] [Google Scholar]
  25. Williams J. H., Li Y. G., Nayak A., Errington M. L., Murphy K. P., Bliss T. V. The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent. Neuron. 1993 Nov;11(5):877–884. doi: 10.1016/0896-6273(93)90117-a. [DOI] [PubMed] [Google Scholar]
  26. Wolf G., Würdig S., Schünzel G. Nitric oxide synthase in rat brain is predominantly located at neuronal endoplasmic reticulum: an electron microscopic demonstration of NADPH-diaphorase activity. Neurosci Lett. 1992 Nov 23;147(1):63–66. doi: 10.1016/0304-3940(92)90775-3. [DOI] [PubMed] [Google Scholar]

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