To NO or not to NO: 'where?' is the question

Histol Histopathol. 2004 Apr;19(2):585-605. doi: 10.14670/HH-19.585.


Nitric oxide (NO) is a gaseous radical with unique biological functions essential for the cardiovascular system, host defense and neuro-transmission. For two decades it was thought that NO was able to diffuse freely across relatively long distances and to traverse major parts of the cell, if not multiple cell layers. However, NO has been proven to be extremely reactive: it reacts with other reactive oxygen species, heavy metals, as well as with cysteine and tyrosine residues in proteins. In accordance, it is now widely accepted that once NO is generated, it is very short-lived and diffuses only over a short distance. This urges for the local production of NO and the localization of NO synthases in the proximity of their downstream targets. This review discusses the highly organized localization of NO synthases, with the endothelial isoform (eNOS) as its main focus, since from this synthase most is known about its subcellular localization and regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Communication
  • Cell Nucleus / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Protein Structure, Tertiary
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • Reactive Oxygen Species
  • Nitric Oxide
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III