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Nitric Oxide/Oxidative Stress: Nitric Oxide Synthase (iNOS, bNOS, eNOS)
 | | | Characteristics | Activities | Inhibitors | Related Products
Nitric oxide (•NO), a highly reactive, diffusible, and unstable radical, plays an important role in the regulation of a wide range of physiological processes, including cellular immunity, angiogenesis, neurotransmission, and platelet aggregation. •NO is synthesized from L-arginine by the action of nitric oxide synthase (NOS) in a two-step oxidation process. Free •NO is a transient species with a half-life of only about five seconds. Hence, most studies on •NO action are based on the activity of NOS. •NO can diffuse across the cell membrane and react with a variety of targets. Reaction of •NO with O2 in aqueous solutions produces the relatively unreactive nitrate and nitrite ions as products. However, •NO can rapidly react with superoxide to produce highly reactive peroxynitrite (ONOO-). Almost all biological effects of •NO are achieved either directly or through other reactive nitrogen intermediates.
NOS is known to exist in three isoforms: (a) a soluble constitutively expressed enzyme found in high concentrations in the brain (bNOS; nNOS; or NOS-1), (b) a constitutively expressed endothelial membrane bound enzyme (eNOS, NOS-3), and (c) an inducible enzyme (iNOS or NOS-2) that is associated with the cytotoxic function of macrophages. These three isoforms exhibit similarities in their structure and mechanism of action. Calmodulin is required for the activity of all three isoforms. The activation of the constitutively expressed isoforms requires Ca2+-dependent binding of calmodulin to the enzyme. However,  in the case of iNOS, calmodulin is irreversibly bound to the enzyme and its activity is regulated by its rate of synthesis rather than by Ca2+ concentration. In the absence of calmodulin iNOS is highly unstable. For their catalytic activities NOS isoforms require three distinct domains: (a) a reductase domain, (b) a calmodulin-binding domain, and (c) an oxygenase domain. The reductase domain contains the FAD and FMN moieties. The oxygenase domain, which contains the binding sites for heme, tetrahydrobiopterin, and arginine, catalyzes the conversion of L-arginine to citrulline and •NO. The maximal rate of •NO synthesis is established by the intrinsic maximum ability of the reductase domain to deliver electrons to the heme domain.
Because of the involvement of all the three NOS isozymes in various aspects of signal transduction, NOS inhibitors have gained prominence in the management of ischemic reperfusion injury, hypotensive effects of drugs, and inflammatory response to cytokines.
| | | | Characteristics of various forms of Nitric Oxide Synthase | Enzyme | Gene | Number of Residues | Cellular Localization and Expression | Regulation | nNOS | NOS1 | 1429-1433 | Brain: mainly soluble Skeletal muscle: mainly particulate | Ca2+/CaM | iNOS | NOS2 | 1144-1153 | Variety of cells: mainly soluble | Cytokine-inducible Ca2+-independent | eNOS | NOS3 | 1203-1205 | Vascular endothelial cells and cardiomyocytes: mainly particulate | Ca2+/CaM |
| | | | Biological Activities of Selected Nitric Oxide Synthase Inhibitors (IC50 values in mM) | | | | | | | 1400W | | 50* | 0.007* | 2* | | Aminoguanidine, Hemisulfate | | 526 | 250 | | | 1-Amino-2-hydroxyguanidine, p-Toluensulfate | | | 68 | | | Bromocriptine Mesylate | | | > 100 | 10 | | Dexamethasone | | | 0.005 | | | NG,NG-Dimethyl-L-arginine, Dihydrochloride | | | | | | NG,NG’-Dimethyl-L-arginine, Dihydrochloride | | | | | | Diphenyleneiodonium Chloride | | 0.18 | 0.05 | | | 2-Ethyl-2-thiopseudourea, HBr | | 0.036† | 0.017† | 0.029† | | Haloperidol | | | | 31† | | L-N5-(1-Iminoethyl)ornithine, 2HCl | | 0.5 | 2.2 | 3.9 | | MEG, Hydrochloride | | | | | | S-Methylisothiourea Sulfate (SMT) | | – | 2.0‡ | | | S-Methyl-L-thiocitrulline, 2HCl | | 5.4 | 34 | 0.3 | | NG-Monoethyl-L-arginine, Monoacetate Salt | | | 81 | | | NG-Monomethyl-D-arginine, Monoacetate Salt | | – | – | – | | NG-Monomethyl-L-arginine, Monoacetate (L-NMMA) | | 0.7 | 3.9 | 0.65 | | NG-Nitro-L-arginine Methyl Ester, Hydrochloride | | 0.5 | | | | L-NIL, 2HCl | | - | 3.3 | 92 | | NG-Nitro-L-arginine (L-NNA) | | 0.09† | 8.1† | 0.025† | | 7-Nitroindazole | | 0.8 | 20 | 0.71 | | 7-Nitroindazole, Sodium Salt | | | | | | 7-Nitroindazole, 3-Bromo-, Sodium Salt | | | | | | nNOS Inhibitor I | | 314† | 39† | 0.12† | | 1,3-PBITU, 2HBr | | 9† | 0.047† | 0.25† | | L-Thiocitrulline, 2HCl | | - | 3.6† | 0.06† | | NG-Propyl-L-arginine | | 8.5 | 180 | 0.057 | | SKF-525A, Hydrochloride | | | | 90 | | TRIM | | >1000 | 27 | 28.2 |
| | | | Inhibitors: Nitric Oxide Synthase (iNOS, bNOS, eNOS) |
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| 1400W |
100050 |
| Aminoguanidine, Hemisulfate |
154500 |
| 1-Amino-2-hydroxyguanidine, p-Toluenesulfonate |
155200 |
| Bromocriptine Mesylate |
203850 |
| Chlorpromazine, Hydrochloride |
215921 |
| Dexamethasone |
265005 |
| NG,NG-Dimethyl-L-arginine, Dihydrochloride |
311203 |
| NG,NG′-Dimethyl-L-arginine, Dihydrochloride |
311204 |
| Diphenyleneiodonium Chloride |
300260 |
| 2-Ethyl-2-thiopseudourea, Hydrobromide |
341180 |
| Haloperidol |
371980 |
| L-N5-(1-Iminoethyl)ornithine, Dihydrochloride |
400600 |
| MEG, Hydrochloride |
444600 |
| Melatonin |
444300 |
| S-Methyl-L-thiocitrulline, Dihydrochloride |
472804 |
| S-Methylisothiourea, Sulfate |
466220 |
| NG-Monoethyl-L-arginine, Monoacetate Salt |
475883 |
| NG-Monomethyl-D-arginine, Monoacetate Salt |
475892 |
| NG-Monomethyl-L-arginine, Monoacetate Salt |
475886 |
| L-NIL, Dihydrochloride |
482100 |
| Nitric Oxide Synthase, Inducible, Inhibitor Set |
482760 |
| Nitric Oxide Synthase, Neuronal Inhibitor I |
490070 |
| NG-Nitro-L-arginine |
483120 |
| NG-Nitro-L-arginine Methyl Ester, Hydrochloride |
483125 |
| p-Nitroblue Tetrazolium Chloride |
484235 |
| 7-Nitroindazole |
483400 |
| 7-Nitroindazole, Sodium Salt |
484500 |
| 7-Nitroindazole, 3-Bromo-, Sodium Salt |
203912 |
| 1,3-PBITU, Dihydrobromide |
512774 |
| PPM-18 |
529570 |
| NG-Propyl-L-arginine |
537200 |
| 1-Pyrrolidinecarbodithioic Acid, Ammonium Salt |
548000 |
| SKF-525A, Hydrochloride |
567300 |
| L-Thiocitrulline, Dihydrochloride |
589411 |
| TRIM |
643500 |
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| | | | Other Related Products | Product | | Comments | | Nitric Oxide Synthase, Inducible, Inhibitor Set | | Provided as a 5 vial set. Each set contains: - 5 mg of 1400W (Cat. No. 100050)
- 10 mg of 1-Amino-2-hydroxyguanidine, p-Toluenesulfonate (Cat. No. 155200)
- 100 mg of S-Methylisothiourea Sulfate (Cat. No. 466220)
- 10 mg of L-NIL, Dihydrochloride (Cat. No. 482100)
- 50 mg of 1,3-PBITU, Dihydrobromide (Cat. No. 512774).
| | Nitric Oxide Assay Kit, Colorimetric | | Assay kit useful for the rapid quantitative measurement of total nitric oxide (NO) in aqueous solutions. Each kit can be used to perform up to 40 assays in duplicate. | | Nitric Oxide Assay Kit, Fluorometric | | Assay kit useful for the rapid quantitative measurement of nitric oxide (NO) in aqueous solutions. Each kit can be used to perform up to 240 samples. Minimum detectable quantity of NO2-/NO3- = 10 nM. | | Nitric Oxide Synthase Assay Kit | | Assay kit useful for the rapid quantitative measurement of nitric oxide synthase (NOS) activity in tissues or cellular extracts. Each kit can be used to perform up to 50 assays. | | Nitric Oxide Synthase Assay Kit, Colorimetric | | Assay kit useful for the rapid and accurate measurement of nitric oxide synthase (NOS) activity. Can be used to assay nitrate and nitrite in plasma, serum, urine, and tissue culture medium. | | NOS Inhibitor Set | | Contains: - 20 mg of L-N5-(1-Iminoethyl)ornithine, HCl (Cat. No.
400600) - 10 mg of S-Methyl-L-thiocitrulline, HCl (Cat. No. 472804)
- 25 mg of NG-Monomethyl-L-arginine, Monoacetate Salt (Cat. No. 475886)
- 100 mg of NG-Nitro-L-arginine Methyl Ester, HCl (Cat. No. 483125)
- 100 mg of NG-Nitro-D-arginine Methyl Ester, HCl, 100 mg of 7-Nitroindazole (Cat. No. 483400)
- 10 mg of L-Thiocitrulline, HCl (Cat. No. 589411).
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