Monomethyl L-arginine

Archer, S. L., Hampl, V. N. G., Monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings trouble in paradise, Biochem. Biophys. Res. Commun. 188 (1992), p. 590-596... 

L-NMMA=N -monomethyl-L-arginine L-NAME=N -monomethyl-L-arginine LTP=long-term potentia-... 

Ramagopal, M. W., and Leighton, H. J. (1989). Effects of N -monomethyl-L-arginine on field stimulation-induced decreases in cytosolic Ca levels and relaxation in the rat anococcygeus muscle. Eur. J. Pharmacol. 174, 297-299. 

Bastian, N. R., Xu, S., Shao, X. L., Shelby, J., Granger, D. L., and Hibbs, J. B., Jr. (1994). N omega-monomethyl-L-arginine inhibits nitric oxide production in murine cardiac allografts but does not affect graft rejection. Biochim. Biojjhys. Acta 1226, 225—231. 

Bergmann, L., Kroncke, K.-D., Suschek, C., Kolb, H., and Kolb-Bachofern, V. (1992). Cytotoxic action of lL-1/3 against pancreatic islets is mediated via nitric oxide formation and is inhibited by N -monomethyl-L-arginine. FEES Lett. 299, 103-106. 

L-arginine analogues, such as N -monomethyl-L-arginine (Hibbs et al., 1987b), which acts as an extremely effective and competitive inhibitor of -NO formation. 

Abbreviations used APC, antigen presenting cell CTL, cytolytic T lymphiKyte GvHD, graft versus host disease MLR, mixed leukocyte reaction NMA, NV -monomethyl-L-arginine, N=0, nitric oxide... 

C. T Cell Cytokine Production in Presence and Absence of N°-Monomethyl-L-Arginine... 

Granger, D. L., Hibbs, J. B., Jr., and Broadnax, L. M. (1991). Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral N - -monomethyl-L-arginine.], Immunol. 146, 1294-1302. 

Vffl-Monomethyl-L-arginine (l-NMMA) Competitive inhibitor, binds arginine-binding site in NOS Nonselective NOS inhibitor... 

A -Monomethyl-L-arginine (L-NMMA) NOS inhibition May act as substrate in some tissues... 

BH4 = Tetrahydrobiopterin CAM = Cytotoxic activated macrophage cNOS = Constitutive nitric oxide synthase CPR = Cytochrome P450 reductase EDRF = Endothelial-derived relaxation factor EPR = Electron paramagnetic resonance spectroscopy IL-1 = Interleukin-1 iNOS = Inducible nitric oxide synthase EPS = Lipopolysaccharide, or endotoxin NMMA = ISp-monomethyl-L-arginine NOS = Nitric oxide synthase ROS = Reactive oxygen species SOD = Superoxide dismutase TNF = Tumor necrosis factor. 

Figure 2 Stoichiometry of the enzymatic mechanism of formation of NO, and the structure of a competitive inhibitor, N -monomethyl-L-arginine (NMMA). NO is synthesized by all NOS s by a similar mechanism, involving the NADPH-dependent mixed-function oxidation of a guanidino nitrogen of the amino acid L-arginine (L-arg) to produce L-citrulline (L-cit) and -NO. The nonintegral stoichiometries are explained in the text. NMMA inhibits NOS as a competitive inhibitor...

Calver A, Collier J, Moncada S, Vallance P (1992) Effect of local infusion of N -monomethyl-L-arginine in patients with hypertension. The nitric oxide dilator mechanism appears abnormal J Hypertens 10 1025-1031. 

Heritac ndcaOedro K, LembowiczK, Pytel B (1991) N -monomethyl-L-arginine increases platdet deposition on danuiged endothdium in vivo. A scanning electron microscopy study Thromb Res 64 1-9. 

Billiar, T. R., Curran, R. D., Harbrecht, B. G., Stuehr, D. J., Demetris, A. J., and Simmons, R. L. (1990). Modulation of nitric oxide synthesis in vivo N -Monomethyl-L-arginine inhibits endotoxin-induced nitrite/nitrate biosynthesis while promoting hepatic damage. J. Leukocyte Biol. 48, 568-569. 

Weinberg, J. B., Granger, D. L., Pisetsky, D. S., Seldin, M. F., Misukonis, M. A., Mason, S. N., Pippin, A. M., Ruiz, P., Wood, E. R., and Gilkeson, G. S. (1994). The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease Increased nitric oxide production and nitric oxide synthase expression in MRL-/pr//pr mice, and reduction of spontaneous nephritis and arthritis by orally administered N -monomethyl-L-arginine. J. Exp. Med. 179, 651-660. 

The addition of NBT, which is known to interact with the superoxide anion and is reduced to formazan, led to the concentration-dependent inhibition of NOS activity, with an apparent K of 3-4 p.M (Mittal et al., 1993). The inhibitory effect of NBT was compared with N -monomethyl-L-arginine (NMA), a structural analog of L-arginine. Inclusion of NMA or NBT at 100 fjiM led to the complete inhibition of L-arginine-dependent stimulation of guanylate cyclase activity without any effect on the basal cGMP produc-... 

FIGURE I Effects of superoxide dismutase (SOD), catalase (CAT), heated catalase (CAT-H), nitroblue tetrazolium (NBT), and N"-monomethyl-L-arginine (NMA). Rat brain cytosol was incubated with 100 juM L-arginine and 100 /zM NADPH for 10 min at 37°C. Nitric oxide (NO) synthase activity was determined as an increase in cGMP formation. (Adapted from Mittal, 1993.)... 

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