Nitric oxide synthases in mammals
Biochemical JournalPublished 1 March 1994Open access
Richard G. Knowles, Salvador Moncada
Citations2,760
SJR quartileQ1
SJR score2.06
SNIP0.98
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TL;DR
This review will describe the known biochemical mechanisms involved in the synthesis of NO from L-arginine by the NO synthases and will also describe the nature of these enzymes, their inhibition and their molecular characteristics.
Abstract
Arginine NO-hydroxylase N&-Hydroxyarginine mono-oxygenase NADPH diaphorase Cytochrome c reductase NADPH oxidase 5 Dihydropteridine reductase Arg + NADPH + H+ + 02 -+ HydroxyArg + NADP+ + H20 HydroxyArg + 1(NADPH + H+) + 02 -+ Cit + NO + H20 NitroBlue Tetrazolium (NBT) + NADPH + H+ Reduced NBT + NADP+ Cyt c+ NADPH + H+ -+ Reduced cyt c+ NADP+ NADPH + H+ + 02 H202 + NADP+ 1NADPH + 02 -+ 02 + 1(NADP+
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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2,760 Citations1994Richard G. Knowles, Salvador Moncada
This review will describe the known biochemical mechanisms involved in the synthesis of NO from L-arginine by the NO synthases and will also describe the nature of these enzymes, their inhibition and their molecular characteristics.
NatureEndothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain
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The LancetAccumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure
2,132 Citations1992A. Leone, S. Moncada +3 more
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Proceedings of the National Academy of SciencesNeuronal NADPH diaphorase is a nitric oxide synthase.
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ScienceCloning and Characterization of Inducible Nitric Oxide Synthase from Mouse Macrophages
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NeuroscienceHistochemical mapping of nitric oxide synthase in the rat brain
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British Journal of PharmacologyCharacterization of three inhibitors of endothelial nitric oxide synthase <i>in vitro</i> and <i>in vivo</i>
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Proceedings of the National Academy of SciencesNitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues.
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BiochemistryMacrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate
1,606 Citations1988Michael A. Marletta, Poksyn S. Yoon +3 more
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ScienceMacrophage Cytotoxicity: Role for L-Arginine Deiminase and Imino Nitrogen Oxidation to Nitrite
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An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is shown to cause this pattern of metabolic inhibition in cytotoxic activated macrophages.
Proceedings of the National Academy of SciencesFormation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.
1,449 Citations1989Richard G. Knowles, Miriam Palacios‐Callender +2 more
Results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to the hypothesis that the formation of NO fromL-argInine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase.
Biochemical and Biophysical Research CommunicationsL-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation
1,350 Citations1988Richard Palmer, Daryl D. Rees +2 more
Data indicate that L-arginine is the physiological precursor for the formation of NO which mediates endothelium-dependent relaxation.
Proceedings of the National Academy of SciencesGlucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells.
1,106 Citations1990Marek W. Radomski, Richard Palmer +1 more
The inhibition of the induction of an NO synthase by glucocorticoids is a receptor-mediated event involving the inhibition ofThe synthesis of mRNA for de novo synthesis of this enzyme may contribute to the pathophysiology of immunologically based conditions.
Proceedings of the National Academy of SciencesEndothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform.
989 Citations1992Santiago Lamas, Philip A. Marsden +3 more
The increase in BAEC NO synthase activity induced by tumor necrosis factor alpha is likely to involve posttranscriptional mechanisms or the induction of a distinct endothelial No synthase isoform.
Proceedings of the National Academy of SciencesPurification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells.
983 Citations1991Jennifer S. Pollock, Ulrich Förstermann +5 more
The particulate enzyme responsible for the synthesis of endothelium-derived relaxing factor has been purified from cultured and native (noncultured) bovine aortic endothelial cells and required L-arginine, NADPH, Ca2+, calmodulin, and 5,6,7,8-tetrahydrobiopterin for full activity.
The Journal of ImmunologyL-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells.
937 Citations1987John B. Hibbs, Zdenek Vavrin +1 more
The results show that the inhibitory effect of these guanidino methylated derivatives of L-arginine is highly determined by structure and does not appear to be for protein synthesis, creatine biosynthesis, polyamine biosynthetic, or ADP ribosylation reactions.
European Journal of PharmacologyCorrelation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase
896 Citations1987Martin Feelisch, E. Noack
The release of nitric oxide from organic nitrates is examined by means of a difference-spectrophotometric method and it is found that the results correlated well with the extent of enzyme activation, suggesting both an enzymatic and a non-enzymatic mode of inhibition of enzyme activity does exist.
Journal of Biological ChemistryMolecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.
869 Citations1992Cheryl Lyons, Gregory Orloff +1 more
Cloning of a cDNA encoding the inducible nitric oxide synthase from a murine macrophage cell line, RAW264.7, exposed to interferon-gamma and lipopolysaccharide, identifies shared binding sites for the cofactors NADPH and flavins in the C-terminal half of both proteins and an additional conserved region near the N terminus that may recognize L-arginine and/or contribute to the active site.
Proceedings of the National Academy of SciencesMolecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.
833 Citations1993David A. Geller, Charles J. Lowenstein +8 more
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Biochemical PharmacologyIsoforms of nitric oxide synthase Characterization and purification from different cell types
821 Citations1991Ulrich Förstermann, Harald Schmidt +6 more
Proceedings of the National Academy of SciencesPurification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein.
818 Citations1991Dennis J. Stuehr, Hyong Jin Cho +3 more
Gel filtration chromatography indicated that the induced NO synthase was catalytically competent as a dimer of approximately 250 kDa but could be dissociated into inactive monomers of approximately 130 kDa in the absence of L-arginine, FAD, and tetrahydrobiopterin.
Journal of Biological ChemistryGeneration of superoxide by purified brain nitric oxide synthase.
753 Citations1992Sovitj Pou, Wanida S. Pou +3 more
Using a spin-trapping technique combined with electron spin resonance spectroscopy, it is reported that brain NOS generates superoxide O2-.
Journal of Clinical InvestigationMolecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.
738 Citations1992K. Nishida, David G. Harrison +7 more
The unique features of the endothelial cell NO synthase, particularly in the amino terminal portion of the molecule, may provide for novel regulatory influences of enzyme activity and localization.
Journal of Biological ChemistryMacrophage Oxidation of L-Arginine to Nitric Oxide, Nitrite, and Nitrate
688 Citations1989Mahmoud Tayeh, Michael A. Marletta
The addition of (6R)-tetrahydrobiopterin (BH,) and NADPH led to complete recovery of activity in this desalted protein and the participation of BH4 in this type of oxidative chemistry is consistent with previous characterizations of this cofactor.
The Journal of Experimental MedicineCalmodulin is a subunit of nitric oxide synthase from macrophages.
639 Citations1992H. J. Cho, Q W Xie +5 more
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FEBS LettersWidespread tissue distribution, species distribution and changes in activity of Ca<sup>2+</sup>‐dependent and Ca<sup>2+</sup>‐independent nitric oxide synthases
635 Citations1991Mark Salter, Richard G. Knowles +1 more
The results demonstrate the differential distribution of NOSs in control and endotoxin‐treated animals and emphasize the widespread biological role of nitric oxide (NO).
Journal of Histochemistry & CytochemistryMapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction.
618 Citations1992Harald Schmidt, Gerard D. Gagné +4 more
The findings suggest that NOS-I is the most widely distributed isoform of NOS and, in addition to its neural functions, regulates secretion and non-vascular smooth muscle function.
Proceedings of the National Academy of SciencesCloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.
614 Citations1992Charles J. Lowenstein, C S Glatt +2 more
Macrophage NOS mRNA is strikingly inducible; it is absent in quiescent macrophages or spleen but is prominent 2-6 hr after endotoxin treatment, and the macrophage enzyme displays 50% sequence identity to the neuronal enzyme.
BiochemistryNitric oxide synthase is a cytochrome P-450 type hemoprotein
612 Citations1992Kimberly A. White, Michael A. Marletta
NOS is the first example of a soluble cytochrome P-450 in eukaryotes and the presence of FAD and FMN indicates that this is theFirst catalytically self-sufficient mammalian P- 450 enzyme, containing both a reductase and a heme domain on the same polypeptide.
Biochemical and Biophysical Research CommunicationsA novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells
607 Citations1989Richard Palmer, Salvador Moncada
An enzyme in homogenates of porcine vascular endothelial cells forms L-citrulline from L-arginine, suggesting that it is involved in the formation of nitric oxide by vascular endothelium cells.
Journal of Biological ChemistryCloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.
606 Citations1992Stefan Janssens, Akito Shimouchi +3 more
Isolation of a cDNA encoding a calcium-regulated, constitutively expressed human endothelial NOS, capable of producing EDRF in blood vessels, will accelerate the characterization of the role of this enzyme in normal and abnormal endothelial regulation of vascular tone.
Biochemical and Biophysical Research CommunicationsDexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: An insight into endotoxin shock
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In vitro studies in rings of rat thoracic aorta indicate that prevention of the induction of NO synthase by glucocorticoids may be an important component of their therapeutic action.
Proceedings of the National Academy of SciencesCalmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells.
595 Citations1991Ulrich Förstermann, Jennifer S. Pollock +3 more
It is concluded that endothelial cells contain both cytosolic and particulate enzymes that synthesize EDRF/NO, and both enzymes are regulated by free Ca2+ and, at least in part, by CaM.
Journal of Biological ChemistryN omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine.
571 Citations1991Dennis J. Stuehr, N S Kwon +4 more
Results support a mechanism in which N omega-hydroxy-L-arginine is generated as an intermediate in nitric oxide (.NO) synthesis through an NADPH-dependent hydroxylation of L-argInine.
Journal of Biological ChemistryReduced Biopterin as a Cofactor in the Generation of Nitrogen Oxides by Murine Macrophages
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The major active component in LF was dialyzable, water soluble, and cationic at acidic to neutral pH, and was facilitated by catalytic amounts of H4biopterin.
Biochemical JournalThe effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Specific labelling of a component polypeptide of the oxidase
553 Citations1986Andrew R. Cross, Owen Jones
NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content.
FEBS LettersCloned human brain nitric oxide synthase is highly expressed in skeletal muscle
548 Citations1993Masaki Nakane, Harald Schmidt +3 more
Unexpectedly, messenger RNA levels of this isoform of NO synthase was more abundant in human skeletal muscle than human brain, indicating a possible novel function of NO in skeletal muscle.
Biochemical JournalCa2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase
534 Citations1992Burghard Heinzel, Michael John +3 more
According to these results, activation of brain NO synthase by Ca2+ at subphysiological levels of intracellular L-arginine or H4biopterin may result in the formation of reactive oxygen species instead of NO, and N omega-nitro-substituted L- arginine analogues represent useful tools to effectively block No synthase-catalysed oxygen activation.
Biochemical PharmacologyInhibition of nitric oxide synthesis by methylene blue
527 Citations1993Bernd Mayer, Friedrich Brünner +1 more
Circulation ResearchNG-nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists.
514 Citations1993Iain L. O. Buxton, Dennis J. Cheek +4 more
Test the possibility thatalogues of L-arginine with modifications at the terminal guanidino nitrogen and/or the carboxyl terminus of the molecule are also muscarinic receptor antagonists and produce concentration-dependent contraction of endothelium-denuded rabbit coronary artery as well as isolated strips of canine colonic smooth muscle.
Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjectsMammalian Nitric Oxide Synthases
509 Citations1992Dennis J. Stuehr, Owen W. Griffith
This report summarizes some of the current information regarding NO synthase structure-function, reaction mechanism, control of catalysis, and protein interactions.
FEBS LettersMolecular cloning and characterization of human endothelial nitric oxide synthase
492 Citations1992Philip A. Marsden, Keith Schappert +6 more
Molecular cloning and sequence analysis of human endothelial NO synthase indicated the existence of a family of constitutive NO synthases, and complementary DNA clones predict a protein of 1,203 amino acids sharing 94% identity with the bovine endothelial protein, but only 60% Identity with the rat brain NO synth enzyme isoform.
Journal of Biological ChemistryMolecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase.
468 Citations1992William C. Sessa, Jeffrey K. Harrison +6 more
The molecular cloning of a cDNA encoding the constitutive calcium-calmodulin (Ca2+/CaM)-regulated nitric oxide synthase (ECNOS) is reported, which contains a unique N-myristylation consensus sequence that may explain its membrane localization.
The FASEB JournalInhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs <sup>1</sup>
464 Citations1991Dennis J. Stuehr, O A Fasehun +5 more
The results suggest that NO∗ synthesis in both macrophages and endothelial cells depends on an NADPH‐utilizing flavoprotein, and DPI and its analogs are likely to prove useful in analyzing the physiologic and pathophysiologic roles of NO·.
Biochemical and Biophysical Research CommunicationsGlucocorticoids inhibit the induction of nitric oxide synthase in macrophages
455 Citations1990Michelino Di Rosa, M. W. Radomski +2 more
Part of the anti-inflammatory and immunosuppressive actions of glucocorticoids is due to their inhibition of the induction of the NO synthase, which is suggested to be responsible for the release of NO.
FEBS LettersPurification of a Ca<sup>2+</sup>/calmodulin‐dependent nitric oxide synthase from porcine cerebellum
450 Citations1990Bernd Mayer, Mathias John +1 more
Two NO synthase isoenzymes are postulated: a cytokine‐inducible enzyme in macrophages and a constitutive, Ca2+‐regulated enzyme in various other cells.
Journal of Biological ChemistryTetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle.
442 Citations1992Steven S. Gross, Roberto Levi
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FEBS LettersBrain nitric oxide synthase is a biopterin‐ and flavin‐containing multi‐functional oxido‐reductase
422 Citations1991Bernd Mayer, Mathias John +5 more
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Biochemical JournalDifferential induction of brain, lung and liver nitric oxide synthase by endotoxin in the rat
394 Citations1990Richard G. Knowles, M. J. Merrett +2 more
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European Journal of PharmacologyArginine is a physiological precursor of endothelium-derived nitric oxide
390 Citations1988Harald Schmidt, Heinz Nau +6 more
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British Journal of PharmacologyFeedback inhibition of nitric oxide synthase activity by nitric oxide
390 Citations1993Jamil Assreuy, Fernando Q. Cunha +2 more
The enzyme activity of J774 cells was not restored after the removal of SNAP by gel filtration, suggesting that NO inhibits NO synthase irreversibly.
Biochemical and Biophysical Research CommunicationsCytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages
389 Citations1991Steven S. Gross, Eric Jaffe +2 more
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Biochemical and Biophysical Research CommunicationsAnti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat
387 Citations1990Richard G. Knowles, Mark Salter +2 more
Inhibition of induction of the Ca2(+)-independent NO synthase in vivo may underlie some of the physiological and pharmacological effects of the anti-inflammatory glucocorticoids.
Proceedings of the National Academy of SciencesPurification of a soluble isoform of guanylyl cyclase-activating-factor synthase.
383 Citations1991Harald Schmidt, Jennifer S. Pollock +4 more
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Journal of Biological ChemistryPurification and properties of a new enzyme, N, N-dimethylarginine dimethylaminohydrolase, from rat kidney
363 Citations1989Takuji Ogawa, Masumi Kimoto +1 more
A new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, has been purified to homogeneity from rat kidney and shows the maximum activity at pH 6.5 and requires no cofactor.
Biochemical and Biophysical Research CommunicationsNitric oxide synthase: Irreversible inhibition by L-N -Nitroarginine in brain and
361 Citations1991Mary A. Dwyer, David S. Bredt +1 more
The potent in vivo inhibition of central NO synthase by NO2Arg may facilitate studies of the physiologic function of NO as a neuronal messenger in brain preparations and appear to be irreversible.
Journal of Biological ChemistrySpectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical.
347 Citations1992Dennis J. Stuehr, Masao Ikeda‐Saito
Nitric oxide synthases isolated from brain and cytokine-activated macrophages are FAD- and FMN-containing flavoproteins that display considerable sequence homology to NADPH-cytochrome P-450 reductase, however, the nature of their catalytic centers is unknown.
Biochemical and Biophysical Research CommunicationsCloning of Inducible Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells
321 Citations1993Youichi Nunokawa, Nobuhiro Ishida +1 more
Findings show that the NOS is inducible and could regulate the proliferation of VSMC and the amino acid sequence deduced from the cloned NOS cDNA was distinct from that of the previously reported constitutive types of NOSs, while highly similar to that of macrophage NOS.
Proceedings of the National Academy of SciencesCloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte.
295 Citations1993I. G. Charles, Richard Palmer +6 more
The similarity (88%) between the human chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage suggests that the inducible class of enzyme is conserved between different cell types and across species.
Journal of Biological ChemistryConstitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline.
289 Citations1991Anna Leone, Richard Palmer +4 more
Activated J774 cells form NO from omega-hydroxyl-L-arginine, confirming the proposal that this compound is an intermediate in the biosynthesis of NO, and determining the source of the oxygen in both NO and in citrulline.
The Journal of Experimental MedicineTetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts.
287 Citations1990Gabriele Werner‐Felmayer, Ernst R. Werner +4 more
The results show that intracellular concentrations of tetrahydrobiopterin control the amount of NO2- and NO3- produced in situ and suggest that the role of cytokine-induced tetrahytochemical synthesis is to provide cells with the active cofactor for production of nitrogen oxides.
Biochimica et Biophysica Acta (BBA) - Reviews on BiomembranesThe transport of cationic amino acids across the plasma membrane of mammalian cells
286 Citations1985Morris F. White
Biochemical and Biophysical Research CommunicationsInduction of Nitric Oxide Synthase in Human Chondrocytes
285 Citations1993Richard Palmer, Mark S. Hickery +3 more
Human articular chondrocytes express an inducible NO synthase from the same family as the rabbit chondROcyte and rodent macrophage enzymes, which appears to vary in terms of in vitro Ca(2+)-dependence and sensitivity to glucocorticoids.
Biochemical and Biophysical Research CommunicationsBiosynthesis of endothelium-derived relaxing factor: A cytosolic enzyme in porcine aortic endothelial cells Ca2+-dependently converts L-arginine into an activator of soluble guanylyl cyclase
273 Citations1989Bernd Mayer, Kurt Schmidt +2 more
The results indicate that endothelial cells contain a cytosolic enzyme which is directly or indirectly regulated by Ca2+ and converts L-arginine into a compound which in stimulating soluble guanylyl cyclase behaves similar to endothelium-derived relaxing factor.
BiochemistrySelective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine
272 Citations1993Eric S. Furfine, Marilyn F. Harmon +2 more
NA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 microM) and rapidly reversible and NA was a 300-fold more potent inhibitor of bovine brain cNOS than mousemacrophage iNOS.
Biochemical and Biophysical Research CommunicationsMacrophage and endothelial cell nitric oxide synthesis: Cell-type selective inhibition by NG-aminoarginine, NG-nitroarginine and NG-methylarginine
272 Citations1990Steven S. Gross, Dennis J. Stuehr +4 more
It is reported that L-NG-aminoarginine and L- NG-nitro arginine are about 100-fold more potent than NG-methylarginines in blocking endothelial cell NO and are about equipotent with macrophages whereas NG-Nitroarg inine is much less potent.
Biochemical and Biophysical Research CommunicationsPhosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase
270 Citations1991Masaki Nakane, Jane A. Mitchell +2 more
Findings indicate that brain nitric oxide synthase activity may be regulated not only by Ca2+/calmodulin and several co-factors, but also by phosphorylation.
Biochemical and Biophysical Research CommunicationsConstitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine
255 Citations1992Norma Rogers, Louis J. Ignarro
Observations indicate clearly that NO formed during the NO synthase reaction or added to the enzyme reaction mixture causes a reversible inhibition of No synthase activity, indicating that NO may function as a negative feedback modulator of its own synthesis.
British Journal of PharmacologyIdentification of N‐iminoethyl‐<scp>l</scp>‐ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells
254 Citations1991Thérèse McCall, Martin Feelisch +2 more
The rapid uptake of l‐NIO compared with the other compounds indicates that phagocytic cells have different uptake mechanisms for l‐arginine analogues, and indicates that l‐nIO is a novel, potent, rapid in onset and irreversible inhibitor of NO synthase in phagocytes.
Journal of Biological ChemistryL-citrulline production from L-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen.
244 Citations1990N S Kwon, C F Nathan +4 more
Results indicate that the ureido oxygen of the L-citrulline product of macrophage NO.synthase derives from dioxygen and not from water.
Journal of Biological ChemistryPurification of nitric oxide synthase from rat macrophages
242 Citations1991Yoshiki Yui, Ryuichi Hattori +4 more
The macrophage nitric oxide synthase (an inducible enzyme) seems to be different from the cerebellar and endothelial enzyme (a constitutive enzyme) because of the lack of Ca2+ and calmodulin.
Biochemical and Biophysical Research CommunicationsNitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands
236 Citations1989Miriam Palacios‐Callender, Richard G. Knowles +2 more
Results indicate that rat and bovine adrenal cytosol contains an L-arginine:NO synthase, which was NADPH- and Ca(2+)-dependent and was inhibited by several L- arginine analogues.
Biochemical JournalKinetic characteristics of nitric oxide synthase from rat brain
204 Citations1990Richard G. Knowles, Miriam Palacios‐Callender +2 more
The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme.
Biochemical and Biophysical Research CommunicationsEndothelial cells metabolize NG -monomethyl-L-arginine to L-citrulline and subsequently to L-arginine
185 Citations1990Markus Hecker, Jane A. Mitchell +4 more
N omega-nitro-L-arginine (NO2Arg), a more potent inhibitor of EDRF synthesis in vitro, was significantly more potent than MeArg in inhibiting the endothelium-dependent relaxation of rabbit aorta induced by acetylcholine and the pressor effect of NO2Arg was significantly larger and longer lasting than that of MeArg.
Biochemical and Biophysical Research CommunicationsNitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine
180 Citations1992Margaret A. Bush, Norma González +2 more
Observations indicate clearly that NO and citrulline are formed in equimolar quantities from L-arginine by the constitutive isoform of NO synthase from rat cerebellum.
Journal of Biological ChemistryCationic amino acid transport into cultured animal cells. I. Influx into cultured human fibroblasts.
180 Citations1982Morris F. White, Gian C. Gazzola +1 more
Uptake of cationic substrates by System y+ is Na+-independent, pH-insensitive, stereoselective, and inhibitable by neutral amino acids in the presence of Na+.
Biochemical and Biophysical Research CommunicationsInducible cytosolic enzyme activity for the production of nitrogen oxides from L-arginine in hepatocytes
179 Citations1990Timothy R. Billiar, Ronald Curran +4 more
Results show the presence of inducible cytosolic enzyme activity for nitrogen oxide synthesis in hepatocytes, which is distinct from nonparenchymal cell NO.
Histochemistry and Cell BiologyImmunological detection of nitric oxide synthase(s) in human tissues using heterologous antibodies suggesting different isoforms
173 Citations1992D.R. Springall, V. Riveros‐Moreno +6 more
Findings support the contention that the endothelial enzyme is a different form with partial homology to that in nerves and also provide an anatomical distribution of NO synthase isoforms in human endothelium.
British Journal of PharmacologyIdentification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell<scp>l</scp>‐arginine transporter
171 Citations1992Richard Bogle, Salvador Moncada +2 more
The ability to modulate selectively endothelial cell l‐arginine transport or NO synthase activity will allow further characterization of the arginine transporter and its role in regulating NO biosynthesis.
Circulation ResearchMutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein.
166 Citations1993William C. Sessa, Cynthia M. Barber +1 more
N-myristoylation is necessary for the membrane localization of ECNOS and may be of special significance for the basal or flow-induced production of NO by the endothelium.
Biochemical JournalTetrahydrobiopterin-dependent formation of endothelium-derived relaxing factor (nitric oxide) in aortic endothelial cells
163 Citations1992Kurt Schmidt, Ernst R. Werner +3 more
Data indicate that the formation of EDRF strictly depends on the presence of intracellular H4biopterin, which, in addition to Ca2+, may represent a further physiological and/or pathophysiological regulatory of endothelial NO synthases.
Proceedings of the National Academy of SciencesTetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine.
161 Citations1991J. Giovanelli, Kenneth L. Campos +1 more
The combined results exclude H4B as a stoichiometric reactant and suggest that H4 B enhances product formation by protecting enzyme activity against progressive loss, and preliminary studies indicate that the decreased activity in the absence of added H 4B does not depend on catalytic turnover of the enzyme.
European Journal of ImmunologyInduction of nitric oxide synthase in rat peritoneal neutrophils and its inhibition by dexamethasone
160 Citations1991Thérèse McCall, Richard Palmer +1 more
Rat peritoneal polymorphonuclear leukocytes elicited with oyster glycogen contain a Ca2+‐independent nitric oxide (NO) synthase which is induced in vivo in a time‐dependent manner and IFN‐γ and TNF‐α synergized to increase further the expression of NO synthase.
Biochemical and Biophysical Research CommunicationsSynthesis of nitrogen oxides from L-arginine by macrophage cytosol: Requirement for inducible and constitutive components
150 Citations1989Dennis J. Stuehr, Nyoun Soo Kwon +4 more
The enzymatic system involved in nitric oxide synthesis by murine macrophages consists of at least one inducible and two constitutive components.
Biochemical JournalBrain nitric oxide synthase is a haemoprotein
148 Citations1992Peter Klatt, Kurt Schmidt +1 more
In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis.
Naunyn-Schmiedeberg s Archives of PharmacologyNitric oxide synthesis in endothelial cytosol: Evidence for a calcium-dependent and a calcium-independent mechanism
148 Citations1989Alexander M�lsch, E. Bassenge +1 more
A calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells is suggested, suggesting a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells.
Archives of Biochemistry and BiophysicsMetabolism of NG,NG- and NG,NG-dimethylarginine in rats
138 Citations1987Tadashi Ogawa, Masumi Kimoto +2 more
Findings show that both dimethylarginines are metabolized by a pathway forming the corresponding alpha-ketoacid analogs and the oxidatively decarboxylated products of the alpha- ketoacids in addition to the N alpha-acetyl conjugates identified previously.
Journal of Medicinal ChemistryIrreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation
128 Citations1993Paul L. Feldman, Owen W. Griffith +2 more
The data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA, which accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.
Proceedings of the National Academy of SciencesBiosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.
120 Citations1983Charles A. Nichol, C L Lee +3 more
Mammalian cells and tissues were found to have two pathways for the biosynthesis of tetrahydrobiopterin (BH4): the conversion of GTP to BH4 by a methotrexate-insensitive de novo pathway and a pterin salvage pathway dependent on dihydrofolate reductase.
Biochemical JournalSpecific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium
116 Citations1977C I Ragan, David P. Bloxham
NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively) and the label associated with this polypeptide was of limited stability, especially at lower pH.
Biochemical and Biophysical Research CommunicationsCytochrome P450 catalyzes the oxidation of Nω-hydroxy-L-arginine by NADPH and O2 to nitric oxide and citrulline
115 Citations1992Jean‐Luc Boucher, Agnès Genet +4 more
Results show that the oxygenation of NOHA by NADPH and O2 with formation of citrulline and NO can be efficiently catalyzed by cy tochromes P450 (with rates up to 1.5 turnovers per min for the cytochromes of the 3A subfamily).
Biochemical and Biophysical Research CommunicationsPurification and characterization of a human NO synthase
115 Citations1991Harald Schmidt, Ferid Murad
Biochemical and Biophysical Research CommunicationsHepatocytes and Macrophages Express an Identical Cytokine-Inducible Nitric Oxide Synthase Gene
112 Citations1993ER Wood, Hillard Berger +2 more
The predicted amino acid sequence of rat hepatocyte inducible NOS is 94% identical with that from the mouse macrophage cell line, RAW264, and differences are most likely the result of species variability which suggests that hepatocytes and macrophages express the same NOS gene upon induction.
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