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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