ABSTRACT
The inducible and constitutive nitric oxide synthases from liver and brain, respectively, have consensus calmodulin-binding sites. Activation of the soluble guanylate cyclase, which requires a nitric oxide-heme complex for full activity, is considered the principal target for intracellular and intercellular communication with nitric oxide and its thiol-bound derivatives. The nitric oxide produced by macrophages and neutrophils attacks the nonheme-iron-sulfur protein and the thioredoxin-dependent ribonucleotide reductase, which is the rate-limiting enzyme of DNA synthesis, in target cells as well as those of the macrophages, themselves. Nitric oxide, either added exogenously or generated by stimulation with gamma-interferon and LPS, results in apoptosis, or programmed cell death in murine peritoneal macrophages. Snyder has said that nitric oxide synthase is one of the most sensitive enzymes in biology in keeping with its responsibility for fine-tuning the levels of a major physiologic mediator. Gamma radiation stimulated the production of nitric oxide in liver, intestine, kidney, lung, brain, spleen, and heart.
