One of the major mechanism through which the effects of Nitric Oxide are mediated the production of the second messenger cyclic GMP (cGMP). Nitric Oxide can stimulate production of cGMP by interacting with the haem group of the enzyme souble guanylate cyclase (sGC). This interaction allows sGC to convert GTP into cGMP.
Once produced cGMP can have a number of effects in cells, but many of those effects are mediated through the activation of protein kinase G (PKG). Active PKG is ultimately responsible for many of the effects of Nitric Oxide including its effects on blood vessel relaxation (vasodilation). Activation of PKG by cGMP leads to activation of myosin phosphatase which in turn leads to release of calcium from intracellular stores in smooth muscle cells. This in turn leads to relaxation of the smooth muscle cells. In the case of vasodilation the Nitric Oxide is originally produced in the neighbouring endothelial cells before diffusing into the smooth muscle cells where it actiavtes sGC and cGMP production.
PKG can also have other effects in cells, for example by activating a number of transcription factors which can lead to changes in gene expression which in turn can alter the response of the cell to a variety of stimuli.
cGMP can also be converted back to GTP by proteins known as phosphodiesterases. Conversion of cGMP to GTP effectively blocks further Nitric Oxide signalling. There are now several drugs which function as phosphodiesterase inhibitors and can restore Nitric Oxide / cGMP signalling. Perhaps the best known of this class of drugs is Viagra.
Website by Phil Dash