Localisation of Nitric Oxide Synthases in the Lung

Nitric oxide synthases (NOSs) had been localised in neuronal and non-neuronal tissues for many years before they had been identified. This paradox was possible, because the histochemical technique of NADPH-diaphorase staining had been used to label subpopulations of neurons without knowing what their function was. About 25 years after the first description of the NADPH-diaphorase histochemistry, it became clear that the neurons labeled with this histochemical technique were identical to the neurons immunoreactive for neuronal NOS. Also the other isoforms that were cloned and sequenced from endothelial cells and macrophages display NADPH-diaphorase activity. Since the domain that generates nitric oxide (NO) from L-arginine is different from the domain of the enzyme that is responsible for the NADPH-diaphorase activity, which has also been found in other enzymes, it has been concluded that the NADPH-diaphorase shows a more widespread distribution than the NOS isoforms. However, each of the three isoforms of NOS has subsequently been found in several cells types other than the tissues from which they had originally been cloned. Thus, in some cell types in the respiratory tract the presence of all isoforms has been reported. Similarly, the initial discrimination between constitutive and inducible isoforms is less distinct than originally thought, since a constitutive expression of inducible NOS and an induction of the constitutive isoforms has been demonstrated.