Pharmacology of nitric oxide (NO)
Nitric oxide is a mediator that is very different from any other hormones and transmitters. Three key properties of NO are important to its unique mode of signal transmis-sion:
• NO is a very small molecule and permeates cell mem-branes with ease – its membrane permeability is compa-rable to that of oxygen.
• It binds very fast and avidly to heme, as both O2 and CO do as well. Its affinity for heme is higher than that of O2 but lower than that of CO. Binding of NO to heme is at the heart of its major established signalling mech-anism.
• NO is a radical (·N=O) and therefore quite reactive. It can react with molecular oxygen and various reactive oxygen species. The ensuing products in turn may react with amino acid side chains in proteins, leading to S-ni-trosylation of cysteines and O-nitrosylation of tyrosines. The significance of protein nitrosylation in signalling is still a matter of debate; we will look at some experimen-tal data below.
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