Nitric oxide synthase inducible form

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

The synthesis of NO requires merely one step the conversion of L-arginine into NO and citrulline. This conversion is catalyzed by the nitric oxide synthase (NOS) enzyme. Three distinct isoforms of the NOS enzyme have been cloned Isoform I (nNOS chromosome 12) is a Ca -dependent neuronal form of the enzyme Isoform n (mNOS or iNOS chromosome 17) is a Ca +-independent macrophage inducible form of the enzyme found in microglia Isoform III (eNOS, chromosome 7) is a Ca +-dependent form found in the endothelial cells that line blood vessels. Since NO is an extremely important messenger substance, the NOS enzyme is exquisitely regulated by processes such as phosphorylation and hormonal control. 

The molecular mechanism linking the inflammatory response to redox equilibria and modification of nitric oxide production will be explored in an animal model system of septic shock, a generalized inflammation induced by bacterial lipopolisaccharide (LPS). It is known that endotoxemia induces a complex interplay between the activation of nuclear transcription factors such as nuclear factor kappa B (NFkB) and a cascade-activation of various enzymatic activities, mostly mediators of the inflammatory response with particular attention to the variation of the inducible form of nitric oxide synthase (iNOS). 

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

Nitric oxide (NO) is a short-acting, potent vasodilator derived from the enzymatic oxidation of arginine. Its production is under control of nitric oxide synthase (NOS). This enzyme is present (expressed) in two forms a constitutive form (ecNOS) and an inducible form (iNOS). Small amounts of NO normally are produced by the vascular endothehum under the control of ecNOS for the physiologic control of vascular tone and blood flow distribution. Under pathophysiologic... 

Abbreviations Con A, concanavalin A CTL, cytotoxic T lymphocytes IL, interleukin iNOS, inducible nitric oxide synthase KLH, keyhole-limpet hemocyanin LAK, lymphokine-activated killer cell NHEK, normal human epidermal keratinocyte NK, natural killer cell PFC, plaque-forming cell SRBC, sheep red blood cell TNF, tumor necrosis factor. 

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