Skip to main content
SpringerLink
Log in

Studies on the localization and expression of nitric oxide synthase using histochemical techniques

  • Review
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

This review provides an update on the variety of histochemical techniques available for the cellular localization and expression of nitric oxide synthase in formalin-fixed tissue sections. The techniques of immunohistochemistry and NADPH-diaphorase histochemistry are discussed and the suitability of various types of probes and reporters which are useful forin situ detection of nitric oxide synthase mRNA expression are assessed. Figures are also included which illustrate the techniques described and protocols forin situ hybridization and NADPH-diaphorase histochemistry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bredt,D. S. &Snyder,S. H. (1990) Isolation of nitric oxide synthase, a calmodulin-requiring enzyme.Proc. Natl Acad. Sci. USA 87, 682–5.

    PubMed  CAS  Google Scholar 

  • Bredt,D. S. &Snyder,S. H. (1992) Nitric oxide a novel neuronal messenger.Neuron 8, 3–11.

    Article  PubMed  CAS  Google Scholar 

  • Bredt,D. S.,Hwang,P. M.,Glatt,C. E.,Lowenstein,C.,Reed,R. R. &Snyder,S. H. (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase.Nature 351, 714–8.

    Article  PubMed  CAS  Google Scholar 

  • Charles,I. G.,Palmer,R. M. J.,Hickery,M. S.,Bayliss,M. T.,Chubb,A. P.,Hall,V. S.,Moss,D. W. &Moncada,S. (1992) Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte.Proc. Natl Acad. Sci. USA 90, 11419–23.

    Google Scholar 

  • Endoh,M.,Maiese,K.,Pulsinelli,W. A. &Wagner,J. A. (1993) Reactive astrocytes express NADPH diaphorase in vivo after transient ischemia.Neurosci. Lett. 154, 125–8.

    Article  PubMed  CAS  Google Scholar 

  • Geller,D. A.,Lowenstein,C. J.,Shapiro,R. A.,Nussler,A. K.,Di Silvio,M.,Wang,S. C.,Nakayama,D. K.,Simmons,R. L.,Snyder,S. H. &Billiar,T. R. (1993) Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.Proc. Natl Acad. Sci. USA 90, 3491–5.

    PubMed  CAS  Google Scholar 

  • Hope,B. T., &Vincent,S. R. (1989) Histochemical characterization of neuronal NADPH-diaphorase.J. Histochem. Cytochem. 37, 653–61.

    PubMed  CAS  Google Scholar 

  • Janssens,S. P.,Shimouchi,A.,Quertermous,T.,Bloch,D. B. &Bloch,K. D. (1992) Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.J. Biol. Chem. 267, 14519–22.

    PubMed  CAS  Google Scholar 

  • Kadowaki,K.,Kishimoto,J.,Leng,G. &Emson,P. C. (1994) Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion.Endocrinology 134, 1011–7.

    Article  PubMed  CAS  Google Scholar 

  • Kishimoto,J.,Keverne,E. B.,Hardwick,J. &Emson,P. C. (1993) Localization of nitric oxide synthase in the mouse olfactory and vomeronasal system: a histochemical, immunological andin situ hybridization study.Eur. J. Neurosci. 5, 1684–94.

    PubMed  CAS  Google Scholar 

  • Kiyama,H.,McGowan,E. M. &Emson,P. C. (1991) Co-expression of cholecystokinin mRNA and tyrosine hydroxylase mRNA in populations of rat substantia nigra cells; a study using a combined radioactive and non-radioactivein situ hybridization procedure.Mol. Brain Res. 9, 87–93.

    PubMed  CAS  Google Scholar 

  • Knowles,R. G. &Moncada,S. (1992) Nitric oxide as a signal in blood vessels.Trends Biochem. Sci. 17, 399–402.

    Article  PubMed  CAS  Google Scholar 

  • Lamas,S.,Marsden,P. A.,Li,G. K.,Tempst,P., &Michel,T. (1992) Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform.Proc. Natl Acad. Sci. USA 89, 6348–52.

    PubMed  CAS  Google Scholar 

  • Lowenstein.,C. J.,Glatt.,C. S.,Bredt,D. S., &Snyder,S. H. (1992) Cloned and expressed macrophage nitric oxide synthase contrasts with brain enzyme.Proc. Natl Acad. Sci. USA 89, 6711–5.

    PubMed  CAS  Google Scholar 

  • Lyons,C. R.,Orloff,G. J. &Cunningham,J. M. (1992) Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.J. Biol. Chem. 267, 6370–4.

    PubMed  CAS  Google Scholar 

  • Marletta,M. A.,Yoon,P. S.,Iyengar,R.,Leaf,C. D. &Wishnok,J. S. (1988) Macrophage oxidation ofl-arginine to nitrite and nitrate-nitric-oxide is an intermediate.Biochemistry 27, 8706–11.

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto,T.,Nakane,M.,Pollock,J. S.,Kuk,J. E. &Forstermann,U. (1993) A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative.Neurosci. Lett. 155, 61–4.

    Article  PubMed  CAS  Google Scholar 

  • Moncada,S.,Radomski,M. W. &Palmer,R. M. J. (1988) Endothelium-derived relaxing factor: Identification as nitric oxide and role in the control of vascular tone and platelet function.Biochem. Pharmacol. 37, 2495–501.

    Article  PubMed  CAS  Google Scholar 

  • Norris,P. J.,Hardwick,J. &Emson,P. C. (1994) Localization of NADPH cytochrome P-450 oxido-reductase in the rat brain by immunohistochemistry andin situ hybridization and a comparison with the distribution of neuronal NADPH-diaphorase staining.Neuroscience 61, 331–50.

    Article  PubMed  CAS  Google Scholar 

  • Nunez,D. J.,Davenport,A. P.,Emson,P. C. &Brown,M. J. (1990) A quantitativein situ hybridization method using computer-assisted image analysis. Validation and measurement of atrial-natriuretic factor in the rat heart.Biochem. J. 263, 121–7.

    Google Scholar 

  • Regidor,J.,Montesdeoca,J.,Ramirezgonzalez,J. A.,Hermandezurquia,C. M. &Divac,I. (1993) Bilateral induction of NADPH-diaphorase activity in neocortical and hippocampal-neurones by unilateral injury.Brain Res. 631, 171–4.

    Article  PubMed  CAS  Google Scholar 

  • Sambrook,J.,Fritsch,E. F. &Maniatis,T. (1989) Detection and analysis of proteins expressed from cloned genes. InMolecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Sessa,W. C.,Harrison,J. K.,Barber,C. M.,Zeng,D.,Durieux,M. E.,D'angelo,D. D.,Lynch,K. R. &Peach,M. J. (1992) Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase.J. Biol. Chem. 267, 15274–6.

    PubMed  CAS  Google Scholar 

  • Snyder,S. H. &Bredt,D. S. (1991) Nitric oxide as a neuronal messenger.Trends Pharmacol. Sci. 12, 125–8.

    Article  PubMed  CAS  Google Scholar 

  • Thomas,E. &Pearse,A. G. E. (1964) The solitary active cells. Histochemical demonstration of damage resistant nerve cells with the a TPN-diaphorase action.Acta Neuropathol. 3, 238–49.

    Article  Google Scholar 

  • Verma,A.,Hirsch,D. J.,Glatt,C. E.,Ronnett,G. V. &Snyder,S. H. (1993) Carbon monoxide: a putative neural messenger.Science 259, 381–4.

    PubMed  CAS  Google Scholar 

  • White,K. A. &Marletta,M. A. (1992) Nitric Oxide Synthase is a Cytochrome P-450 type Hemoprotein.Biochemistry 31, 6627–31.

    PubMed  CAS  Google Scholar 

  • Xie,Q-W.,Cho,H. J.,Calaycay,J.,Mumford,R. A.,Swiderek,K. M.,Lee,T. D.,Ding,A.,Troso,T. &Nathan,C. (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages.Science 256, 225–8.

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. C. A. Scorer

    Present address: Department of Molecular and Cell Biology, Wyeth Research (UK) Ltd, Huntercombe Lane South, SL6 0PH, Taplow, Maidenhead, Berks, UK

Authors and Affiliations

  1. MRC Molecular Neuroscience Group; Department of Neurobiology, The Babraham Institute, CB2 4AT, Babmham, Cambridge, UK

    P. J. Norris & P. C. Emson

  2. The Wellcome Foundation, Wellcome Research Laboratories, Langley Court, South Eden Park Road, BR3 3BS, Beckenham, Kent, UK

    I. G. Charles & C. A. Scorer

Authors
  1. P. J. Norris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. G. Charles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. A. Scorer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. C. Emson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norris, P.J., Charles, I.G., Scorer, C.A. et al. Studies on the localization and expression of nitric oxide synthase using histochemical techniques. Histochem J 27, 745–756 (1995). https://doi.org/10.1007/BF02388300

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02388300

Keywords

Search

Navigation