Nitric oxide synthase constitutive

Radomski, M.W., Palmer, R.M. and Moncada, S. (1990). Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc. Natl Acad. Sci. USA 87, 10043-10047. 

NOD Non-obese diabetic NOS Nitric oxide synthase c-NOS Ca -dependent constitutive form of NOS... 

C.M. Tolias, J.C. McNeil, J. Kazlauskate, and E.W. Hillhouse, Superoxide generation from constitutive nitric oxide synthase in astrocytes in vitro regulates extracellular nitric oxide availability. Free Radical Biol. Med. 26, 99-106 (1999). 

Sheta, E. A., McMillan, K., Masters, B. S., Evidence for a bidomain structure of constitutive cerebellar nitric oxide synthase, J. Biol. Chem. 269 (1994), p. 15147-15153... 

Raman, C. S., Li, H., Martasek, P., Kral, V., Masters, B. S., Poulos, T. L., Crystal structure of constitutive endothelial nitric oxide synthase a paradigm for pterin function involving a novel metal center, Cell 95 (1998),... 

I nhibition of constitutive and inducible nitric oxide synthase potential selective inhibition, Anna. 

Schini.V. B., Vanhoutte, P. M., Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta, J. Pharmacol. Exp. Then 261 (1992), p. 553-559... 

Rogers, N. E., Ignarro, L. J., Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine, Biochem. Biophys. Res. Commun. 189 (1992), p. 242—249... 

As shown in Figure 5.5, nitric oxide is synthesized from the amino acid arginine under the influence of nitric oxide synthase (NOS). This enzyme exists in several tissues as either a constitutive or inducible protein (iNOS). 

Angiogenesis inhibition. Cigarette smoke or smoke extract, administered to ulcerated rats once daily for 3 days, produced concomitant and dose-dependent reduction of angiogenesis and constitutive nitric oxide synthase activity . ... 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Lamas, S., Marsden, P. A., Li, G. K., Tempst, P., and Michel, T. (1992). Endothelial nitric oxide synthase Molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc. Natl. Acad. Sci. U.S.A. 89, 6348-6352. 

Leone, A. M., Palmer, R. M., Knowles, R. G., Francis, P. L., Ashton, D. S., and Moncada, S. (1991). Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citruline. J. Biol. Chem. 266, 23790-23795. 

VII. CONSTITUTIVE NITRIC OXIDE SYNTHASE AND INSULIN SECRETION... 

Nitric oxide has multiple functions depending on the amount of nitric oxide generated, the enzymatic source of nitric oxide (inducible versus constitutive), and the site at which nitric oxide is generated. If nitric oxide mediates or participates in IDDM, then inhibition of nitric oxide generation by the inducible isoform of nitric oxide synthase should delay or prevent the onset of IDDM. Many inhibitors have been developed to block nitric oxide synthase activity. 

Ebselen and related compounds, among them carboxylated analog 59 (R = 4-C6H4COOH), have been reported to be inhibitors of constitutive endothelial nitric oxide synthase (ec NOS) [153, 258-260], Selenourea derivatives, among them 2-aminoselenazoline, are potent inhibitors of the iNOS [261],... 

G Cirino. Multiple controls in inflammation. Extracellular and intracellular phospholipase A2, inducible and constitutive cyclooxygenase, and inducible nitric oxide synthase. Biochem Pharmacol 55 105-111, 1998. 

Chatzipanteli K., Wada K., Busto R., and Dietrich W. D. (1999) Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat. J. Neurochem. 72, 2047-2052. 

Invention Significance The endothelial constitutive nitric oxide synthase... 

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