Nitric oxidase synthase

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

Because NO synthases belong to the same superfamily of enzymes as cytochrome P-450, they are able to produce not only nitric oxide (although it is undoubtedly their main function) but also other free radicals, first of all, superoxide. In 1992, Pou et al. [148] showed that brain nitric oxide synthase (NOS I) produced superoxide identified as a DMPO—OOH adduct in a calcium- or calmodulin-dependent manner. This finding was confirmed in numerous studies for all three isoforms of NO synthase. Although the structures of all the three NO oxidase... 

Zhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., Symons, M. C. R., Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity. Biochem. Biophys. Res. Commun. 249 (1998), p. 767—772... 

AC VIII, adenylyl cyclase type VIII BDNF, brain-derived neurotrophic factor CamKII, calcium-calmodulin kinase II GIRK2, G protein-activated inward rectifying potassium 2 MAOA, monoamine oxidase A n.d., not determined NCAM, neural cell adhesion molecule nNOS, neuronal nitric oxide synthase Petl, ETS domain transcription factor tPA, serine protease tissue-plasminogen activator (tPA). t/ > Increase/decrease in anxiety-related behavior. No effect. 

Shiloh, M.U., MacMicking, J.D., Nicholson, S., Brause, J.E., Potter, S., Marino, M., Fang, F., Dinauer, M., Nathan, C. Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase, Immunity 1999, 10, 29-38. 

Loomis ED, Sullivan JC, Osmond DA, Pollock DM, Pollock JS. 2005. Endothelin mediates superoxide production and vasoconstriction through activation of NADPH oxidase and uncoupled nitric-oxide synthase in the rat aorta. J Pharmacol Exp Ther 315 1058-1064. 

Tricyclic thiopyran-2-one derivatives are useful in the development of therapies for the treatment of viral infections and diseases including AIDS <1996USP5504104>. The thiocoumarin 583 has been identified as a weak inhibitor of inducible nitric oxide synthase <2005BMC2723> and the (l,3,4-thiadiazol-5-yl)thiocoumarin 584 is active against monoamine oxidase B in rat brains <1994EPP594036>. 

Kozlovski, V.I., Olszanecki, R., and Chlopicki, S. 2006. Free radicals generated by xan-thine/xanthine oxidase system augment nitric oxide synthase (NOS) and cyclooxygenase (COX)-independent component of bradykinin-induced vasodilatation in the isolated guinea pig heart. Pharmacol. Rep. 58 405—412. 

Tetrahydrobiopterin is not a vitamin, because it can be synthesized from GTP, as shown in Figure 10.2 (Thony et al., 2000). It is the coenzyme for mixed-function oxidases phenylalanine, tyrosine, and tryptophan hydroxylases alkyl glycerol monoxygenase, which catalyzes the cleavage of alkyl glycerol ethers and nitric oxide synthase in the formation of nitric oxide. In addition to its coenzyme role, tetrahydrobiopterin has a direct effect on neurons, acting to stimulate dopamine release via a cAMP-dependent protein kinase and a calcium channel (Koshimura et al., 2000). 

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