In contrast, the immune system produces high concentrations of NO and exploits its reactive properties to combat bacteria, intracellular parasites, viruses and tumor cells. Due to its unstable and membrane diffusible nature, NO differs from other neurotransmitters and hormones in that it is not regulated by storage, release or targeted degradation, but rather solely by synthesis. Because NO acts as a signal in low amounts and a toxin in high amounts, its production is carefully balanced in healthy humans depending on the state of the organism. Pathologies thought to involve too little NO production include hypertension, impotence, arteriosclerosis, and a susceptibility to infection. Diseases linked to excessive NO production include immune-type diabetes, neurotoxicity associated with aneurysm, stroke and reperfusion injury, inflammatory bowel disease, rheumatoid arthritis, cancer, septic shock, multiple sclerosis and transplant rejection.
Excess production appears to cause brain damage from stroke and also inflammatory conditions.
The researchers believe that the unexpected discovery of two adjacent binding sites for the NOS inhibitor imidazole in the active site promises to aid in the design of drugs to modulate NOS activity and prevent NO overproduction. Since the characteristics of NOS inhibition vary among different NOS types, these dual-function inhibitors also may lead to new drugs that target only one of the various forms of NOS, thereby limiting potential side effects. The chemistry NOS uses to produce NO is complicated and unique in biology, and its structure is completely different from other oxygenase enzymes involved in hormone synthesis and the detoxification of harmful compounds. However, a comparison provides insight into the aspects of these enzymes that are key for the similarities and differences in the reactions they catalyze. According to Tainer, this should aid researchers in reproducing these biological reactions in the laboratory for the design of drugs or other desirable compounds.