Nitric oxide in intercellular communication

Nitric oxide (NO) functions as a messenger in transduction of the paracrine signal. It produces a rapid and relatively short-term response in target cells caused by a decrease in the Ca2+ level, as well as longterm effects as a result of induction of certain genes. Synthesis of NO occurs in cells of various types upon arginine oxidation by a specific monooxidase whose activity depends on calmodulin and external stimuli such as interferons, steroids, and tumor necrosis factors and other cytokines. In target cells, NO and its active derivatives, e.g., peroxynitrite, affect proteins containing heme, iron-sulfur centers, and active thiols. NO inhibits iron-sulfur enzymes and activates guanylate cyclase, transcription factors NF-kappa B and AP-1, and a system of MAP proteinases controlled by G protein H-Ras. Its action can initiate different, even opposite, effects in target cells, depending on additional factors of the redox and proliferative status, NO concentration, and other conditions. In addition to cytokines and other tissue hormones, NO influences the effector systems controlling proliferation, apoptosis, and differentiation of cells and their stress resistance.