Gene Symbol: nNOS
Description: nitric oxide synthase 1
Alias: IHPS1, N-NOS, NC-NOS, NOS, bNOS, nNOS, nitric oxide synthase, brain, NOS type I, constitutive NOS, neuronal NOS, nitric oxide synthase 1 (neuronal), peptidyl-cysteine S-nitrosylase NOS1
Species: human
Products:     nNOS

Top Publications

  1. Bredt D, Snyder S. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990;87:682-5 pubmed
    ..The purified enzyme migrates as a single 150-kDa band on SDS/PAGE, and the native enzyme appears to be a monomer. ..
  2. Saitoh F, Tian Q, Okano A, Sakagami H, Kondo H, Suzuki T. NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. J Biol Chem. 2004;279:29461-8 pubmed
    Targeting of neuronal nitric-oxide synthase (nNOS) to appropriate sites in a cell is mediated by interactions with its PDZ domain and plays an important role in specifying the sites of reaction of nitric oxide (NO) in the central nervous ..
  3. McConell G, Bradley S, Stephens T, Canny B, Kingwell B, Lee Young R. Skeletal muscle nNOS mu protein content is increased by exercise training in humans. Am J Physiol Regul Integr Comp Physiol. 2007;293:R821-8 pubmed
    The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS mu. Exercise training increases nNOS mu protein levels in rat skeletal muscle, but data in humans are conflicting...
  4. Kwon O, Hong S, Ramesh G. Diminished NO generation by injured endothelium and loss of macula densa nNOS may contribute to sustained acute kidney injury after ischemia-reperfusion. Am J Physiol Renal Physiol. 2009;296:F25-33 pubmed publisher
    ..No differences were observed in the inducible NOS staining pattern between the two groups. Neuronal NOS staining was rarely observed in the macula densae of subjects but was prominent in control tissues...
  5. Xu K, Huso D, Dawson T, Bredt D, Becker L. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci U S A. 1999;96:657-62 pubmed
    ..Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR ..
  6. Saur D, Vanderwinden J, Seidler B, Schmid R, De Laet M, Allescher H. Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis. Proc Natl Acad Sci U S A. 2004;101:1662-7 pubmed
    ..and gastric-outlet obstruction, is associated with altered expression of neuronal nitric oxide synthase (nNOS)...
  7. Salam M, Bastain T, Rappaport E, Islam T, Berhane K, Gauderman W, et al. Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children. Allergy. 2011;66:412-9 pubmed publisher
    ..Variants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings. ..
  8. Chakrabarti S, Chan C, Jiang Y, Davidge S. Neuronal nitric oxide synthase regulates endothelial inflammation. J Leukoc Biol. 2012;91:947-56 pubmed publisher
    ..However, recent data suggest an important role for nNOS in the endothelium, although little is known about factors regulating this novel eNOS...
  9. DeMeo D, Campbell E, Barker A, Brantly M, Eden E, McElvaney N, et al. IL10 polymorphisms are associated with airflow obstruction in severe alpha1-antitrypsin deficiency. Am J Respir Cell Mol Biol. 2008;38:114-20 pubmed
    ..Haplotype analysis of IL10 SNPs suggested the strongest association with IL10 promoter SNPs. IL10 is likely an important modifier gene for the development of COPD in individuals with severe AAT deficiency. ..

More Information


  1. Hillier B, Christopherson K, Prehoda K, Bredt D, Lim W. Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science. 1999;284:812-5 pubmed
    The PDZ protein interaction domain of neuronal nitric oxide synthase (nNOS) can heterodimerize with the PDZ domains of postsynaptic density protein 95 and syntrophin through interactions that are not mediated by recognition of a typical ..
  2. Kellogg D, Zhao J, Wu Y. Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo. J Physiol. 2008;586:847-57 pubmed
    ..We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming...
  3. Melikian N, Seddon M, Casadei B, Chowienczyk P, Shah A. Neuronal nitric oxide synthase and human vascular regulation. Trends Cardiovasc Med. 2009;19:256-62 pubmed publisher
    ..responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC)...
  4. Wang P, Zhang Q, Tochio H, Fan J, Zhang M. Formation of a native-like beta-hairpin finger structure of a peptide from the extended PDZ domain of neuronal nitric oxide synthase in aqueous solution. Eur J Biochem. 2000;267:3116-22 pubmed
    Neuronal nitric oxide synthase (nNOS) is targeted to the cell membrane via interactions of its extended PDZ domain with PDZ domains of membrane-associated proteins including PSD-95 and alpha1-syntrophin...
  5. Jaffrey S, Snowman A, Eliasson M, Cohen N, Snyder S. CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95. Neuron. 1998;20:115-24 pubmed
    Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations...
  6. Leung T, Liu E, Tang N, Ko F, Li C, Lam C, et al. Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children. Clin Exp Allergy. 2005;35:1288-94 pubmed
    ..Single nucleotide polymorphisms (SNPs) in nitric oxide synthase (NOS) genes have been associated with atopy and exhaled NO concentrations in Caucasians...
  7. Seddon M, Chowienczyk P, Brett S, Casadei B, Shah A. Neuronal nitric oxide synthase regulates basal microvascular tone in humans in vivo. Circulation. 2008;117:1991-6 pubmed publisher
    ..NO production by the endothelial NO synthase (eNOS); however, recent evidence suggests that a neuronal NO synthase (nNOS) may also be expressed in arterial vessels...
  8. Wechsler M, Grasemann H, Deykin A, Silverman E, Yandava C, Israel E, et al. Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. Am J Respir Crit Care Med. 2000;162:2043-7 pubmed
  9. Brenman J, Chao D, Xia H, Aldape K, Bredt D. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell. 1995;82:743-52 pubmed
    Nitric oxide (NO) is synthesized in skeletal muscle by neuronal-type NO synthase (nNOS), which is localized to sarcolemma of fast-twitch fibers. Synthesis of NO in active muscle opposes contractile force...
  10. Chen Z, McConell G, Michell B, Snow R, Canny B, Kemp B. AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Am J Physiol Endocrinol Metab. 2000;279:E1202-6 pubmed
  11. Brenman J, Chao D, Gee S, McGee A, Craven S, Santillano D, et al. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996;84:757-67 pubmed
    Neuronal nitric oxide synthase (nNOS) is concentrated at synaptic junctions in brain and motor endplates in skeletal muscle...
  12. Seddon M, Melikian N, Dworakowski R, Shabeeh H, Jiang B, Byrne J, et al. Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo. Circulation. 2009;119:2656-62 pubmed publisher
    ..reported that human forearm basal microvascular tone in vivo is tonically regulated by neuronal NO synthase (nNOS), in contrast to an acetylcholine-stimulated reduction in tone, which is eNOS dependent...
  13. Golser R, Gorren A, Leber A, Andrew P, Habisch H, Werner E, et al. Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation. J Biol Chem. 2000;275:5291-6 pubmed
    ..310-329) we studied the interaction of the receptor with purified eNOS and neuronal nitric-oxide synthase (type I) (nNOS). The peptide inhibited formation of L-citrulline by eNOS and nNOS with IC(50) values of 10.6 +/- 0.4 microM and 7...
  14. Ali M, Khoo S, Turner S, Stick S, Le Souef P, Franklin P. NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children. Pediatr Allergy Immunol. 2003;14:261-5 pubmed
    ..3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FENO. ..
  15. Han G, Ma H, Chintala R, Miyake K, Fulton D, Barman S, et al. Nongenomic, endothelium-independent effects of estrogen on human coronary smooth muscle are mediated by type I (neuronal) NOS and PI3-kinase-Akt signaling. Am J Physiol Heart Circ Physiol. 2007;293:H314-21 pubmed
    ..techniques to now identify novel targets of estrogen action in HCASMC: type I (neuronal) nitric oxide synthase (nNOS) and phosphatidylinositol 3-kinase (PI3-kinase)Akt...
  16. Rudnick J, Püttmann B, Tesch P, Alkner B, Schoser B, Salanova M, et al. Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest. FASEB J. 2004;18:1228-30 pubmed
    ..linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise ..
  17. Kobayashi Y, Rader E, Crawford R, Iyengar N, Thedens D, Faulkner J, et al. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008;456:511-5 pubmed publisher
    ..in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise...
  18. Christopherson K, Hillier B, Lim W, Bredt D. PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem. 1999;274:27467-73 pubmed
    ..glutamate receptors, suggesting that there is a specific link between these receptors and neuronal NO synthase (nNOS). Here, we find that PSD-95 assembles a postsynaptic protein complex containing nNOS and NMDA receptors...
  19. Firestein B, Bredt D. Interaction of neuronal nitric-oxide synthase and phosphofructokinase-M. J Biol Chem. 1999;274:10545-50 pubmed
    Neurons that express neuronal nitric-oxide synthase (nNOS) are resistant to NO-induced neurotoxicity; however, the mechanism by which these neurons are protected is not clear...
  20. Rodriguez Crespo I, Straub W, Gavilanes F, Ortiz de Montellano P. Binding of dynein light chain (PIN) to neuronal nitric oxide synthase in the absence of inhibition. Arch Biochem Biophys. 1998;359:297-304 pubmed
    ..in a rat hippocampal cDNA library using the yeast two-hybrid system and various neuronal nitric oxide synthase (nNOS) fragments as bait, was reported to be an inhibitor of nNOS (Science 274, 774-778, 1996)...
  21. Venema V, Ju H, Zou R, Venema R. Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. J Biol Chem. 1997;272:28187-90 pubmed
    Neuronal nitric-oxide synthase (nNOS) has been shown previously to interact with alpha1-syntrophin in the dystrophin complex of skeletal muscle...
  22. Tian M, Liu F, Liu H, Zhang Q, Li L, Hou X, et al. Grape seed procyanidins extract attenuates Cisplatin-induced oxidative stress and testosterone synthase inhibition in rat testes. Syst Biol Reprod Med. 2018;64:246-259 pubmed publisher
    ..MT-1: metallothionein-1; NO: nitric oxide; ONOO-: peroxynitrite; NOS: nitric oxide synthases; nNOS: neuronal NOS; iNOS: inducible NOS; eNOS: endothelial NOS; MDA: malondialdehyde; GSH: glutathione; T-AOC: total antioxidant ..
  23. Zhao X, Sun P, Li G, Yi R, Qian Y, Park K. Polyphenols in Kuding tea help prevent HCl/ethanol-induced gastric injury in mice. Food Funct. 2018;9:1713-1725 pubmed publisher
    ..Mn-SOD (manganese-superoxide dismutase), GSH-Px (glutathione peroxidase), neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), messenger RNA (mRNA) and protein in gastric tissue was stronger in the HKTP-treated mice ..
  24. GÄ…dek Michalska A, Tadeusz J, Rachwalska P, Bugajski J. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep. 2013;65:1655-62 pubmed
    ..Neuronal NO synthase (nNOS) modulates learning and memory and is involved in development of neuropsychiatric diseases, including depression...
  25. Mapelli L, Gagliano G, Soda T, Laforenza U, Moccia F, D Angelo E. Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System. J Neurosci. 2017;37:1340-1351 pubmed publisher
    ..large activity fluctuations that shows a prominent expression of NMDA receptors (NMDARs) and nitric oxide synthase (NOS) and is therefore much more suitable for effective NVC...
  26. Zhao X, Liu J, Yang S, Song D, Wang C, Chen C, et al. Ling-Yang-Gou-Teng-decoction prevents vascular dementia through inhibiting oxidative stress induced neurovascular coupling dysfunction. J Ethnopharmacol. 2018;222:229-238 pubmed publisher
    ..LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability...
  27. Weber H, Klamer D, Freudenberg F, Kittel Schneider S, Rivero O, Scholz C, et al. The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis. Eur Neuropsychopharmacol. 2014;24:65-85 pubmed publisher
    ..In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is ..
  28. Kaji I, Akiba Y, Said H, Narimatsu K, Kaunitz J. Luminal 5-HT stimulates colonic bicarbonate secretion in rats. Br J Pharmacol. 2015;172:4655-70 pubmed publisher
    ..Removal of the submucosa or pretreatment with NOS inhibitors enhanced luminal 5-HT-evoked ΔIsc , suggesting that NO synthesized in the submucosa suppresses ..
  29. Díaz D, Murias A, Ávila Zarza C, Muñoz Castañeda R, Aijón J, Alonso J, et al. Striatal NOS1 has dimorphic expression and activity under stress and nicotine sensitization. Eur Neuropsychopharmacol. 2015;25:1683-94 pubmed publisher
    ..In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism...
  30. Sadi A, Afroze T, Siraj M, Momen A, White Dzuro C, Zarrin Khat D, et al. Cardiac-specific inducible overexpression of human plasma membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury. Clin Sci (Lond). 2018;132:641-654 pubmed publisher
    ..Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin...
  31. Fang J, Huang X, Han X, Ouyang X, Fan L, Zhao X, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med. 2018;15:284-295 pubmed publisher
    ..Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284-295. ..
  32. Kozłowska A, Mikołajczyk A, Adamiak Z, Majewski M. Distribution and chemical coding of sensory neurons innervating the skin of the porcine hindlimb. Neuropeptides. 2017;61:1-14 pubmed publisher
    ..calbindin-D28k (CB), pituitary adenylate cyclase-activating polypeptide (PACAP) and neuronal nitric oxide synthase (nNOS). Meanwhile large-sized FB+ perikarya usually expressed SP, CGRP or PACAP...
  33. Rahnama i M, Biallosterski B, Van Kerrebroeck P, van Koeveringe G, Gillespie J, de Wachter S. Distribution and sub-types of afferent fibre in the mouse urinary bladder. J Chem Neuroanat. 2017;79:1-11 pubmed publisher
    ..CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). In the sub-urothelium, different types of afferent nerve fibre were found, i.e...
  34. Hennig G, Gould T, Koh S, Corrigan R, Heredia D, Shonnard M, et al. Use of Genetically Encoded Calcium Indicators (GECIs) Combined with Advanced Motion Tracking Techniques to Examine the Behavior of Neurons and Glia in the Enteric Nervous System of the Intact Murine Colon. Front Cell Neurosci. 2015;9:436 pubmed publisher
    ..We bred several GCaMP3 mice: (1) Wnt1-GCaMP3, all enteric neurons and glia; (2) GFAP-GCaMP3, enteric glia; (3) nNOS-GaMP3, enteric nitrergic neurons; and (4) ChAT-GCaMP3, enteric cholinergic neurons...
  35. La Padula P, Etchegoyen M, Czerniczyniec A, Piotrkowski B, Arnaiz S, Milei J, et al. Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide. Nitric Oxide. 2018;73:52-59 pubmed publisher
    ..Eosin and hematoxiline staining were used for histological studies. Cytosolic expression of HIF1-α, nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats...
  36. Beck M, Schlabrakowski A, Schrödl F, Neuhuber W, Brehmer A. ChAT and NOS in human myenteric neurons: co-existence and co-absence. Cell Tissue Res. 2009;338:37-51 pubmed publisher
    ..excitatory and inhibitory neurotransmitters: choline acetyltransferase (ChAT) or neuronal nitric oxide synthase (NOS). Two minor groups of myenteric neurons contain either both enzymes or neither...
  37. Agurto A, Vielma A, Cadiz B, Couve E, Schmachtenberg O. NO signaling in retinal bipolar cells. Exp Eye Res. 2017;161:30-35 pubmed publisher
    ..synthesis in dark-adapted retinas, through labeling with the NO marker DAF-FM, with neuronal nitric oxide synthase (nNOS) and inducible NOS expression, and presence of the NO receptor soluble guanylate cyclase in bipolar cells...
  38. Torres da Silva K, Da Silva A, Barioni N, Tessarin G, De Oliveira J, Ervolino E, et al. Neurochemistry study of spinal cord in non-human primate (Sapajus spp.). Eur J Histochem. 2016;60:2623 pubmed publisher
    ..Immunohistochemistry data revealed neuronal nitric oxide synthase (nNOS) immunoreactivity  in neuronal somata and in fibers of laminae I, II, III, VII, VIII, X and IML; choline ..
  39. Wynia Smith S, Smith B. Nitrosothiol formation and S-nitrosation signaling through nitric oxide synthases. Nitric Oxide. 2017;63:52-60 pubmed publisher
    ..NO is produced in mammals by three nitric oxide synthase (NOS) isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS)...
  40. Syed M, Choo Wing R, Homer R, Bhandari V. Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs. PLoS ONE. 2016;11:e0147588 pubmed publisher
    The role of vascular endothelial growth factor (VEGF)-induced 3 different nitric oxide synthase (NOS) isoforms in lung development and injury in the newborn (NB) lung are not known...
  41. Nieto C, Cabildo M, Cornago M, Sanz D, Claramunt R, Torralba M, et al. Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin. Molecules. 2015;20:15643-65 pubmed publisher
    ..The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented...
  42. Mitrou N, Morrison S, Mousavi P, Braam B, Cupples W. Transient impairment of dynamic renal autoregulation in early diabetes mellitus in rats. Am J Physiol Regul Integr Comp Physiol. 2015;309:R892-901 pubmed publisher
    ..Furthermore nitric oxide synthesis (NOS) inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) significantly improved autoregulation in early DM but ..
  43. Lin S, Wu F, Wei M, Shen L. Depletion of arginine by recombinant arginine deiminase induces nNOS-activated neurotoxicity in neuroblastoma cells. Biomed Res Int. 2014;2014:589424 pubmed publisher
    The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders...
  44. Kishimoto J, Spurr N, Liao M, Lizhi L, Emson P, Xu W. Localization of brain nitric oxide synthase (NOS) to human chromosome 12. Genomics. 1992;14:802-4 pubmed
    ..This rat cDNA was used to isolate a human nitric oxide synthase (NOS) cDNA from a human cerebellum cDNA library. The human cDNA clone containing 1...
  45. Mulhall J, Muller A, Donohue J, Mullerad M, Kobylarz K, Paduch D, et al. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med. 2008;5:1126-1136 pubmed publisher
    ..Immunohistochemical antibody staining was performed for endothelial (CD31 and eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed to analyze the AKT/eNOS pathway...
  46. Solhaug M, Kullaprawithaya U, Dong X, Dong K. Expression of endothelial nitric oxide synthase in the postnatal developing porcine kidney. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1269-75 pubmed
    ..The purpose of this study was to characterize eNOS expression during maturation and compare this to neuronal NOS (nNOS)...
  47. Pedersen N, Ferrari L, Venner A, Wang J, Abbott S, Vujovic N, et al. Supramammillary glutamate neurons are a key node of the arousal system. Nat Commun. 2017;8:1405 pubmed publisher
    ..Activation of SuMNos1/Vglut2 neurons potently drives wakefulness, whereas inhibition reduces REM sleep theta activity. These results identify SuMvglut2 neurons as a key node of the wake-sleep regulatory system. ..
  48. Sampaolo S, Liguori G, Vittoria A, Napolitano F, Lombardi L, Figols J, et al. First study on the peptidergic innervation of the brain superior sagittal sinus in humans. Neuropeptides. 2017;65:45-55 pubmed publisher
    ..The neurotransmitters calcitonin gene related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY) were found in ..
  49. Kumagai Y, Hayashi T, Miyauchi T, Endo A, Iguchi A, Kiriya Sakai M, et al. Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation. Am J Physiol Regul Integr Comp Physiol. 2001;281:R25-30 pubmed
    ..an environmental chemical contained in diesel exhaust particles, suppresses neuronal nitric oxide synthase (nNOS) activity by shunting electrons away from the normal catalytic pathway, it was hypothesized that phenanthraquinone ..
  50. Retz W, Reif A, Freitag C, Retz Junginger P, Rösler M. Association of a functional variant of neuronal nitric oxide synthase gene with self-reported impulsiveness, venturesomeness and empathy in male offenders. J Neural Transm (Vienna). 2010;117:321-4 pubmed publisher
    ..The findings give additional evidence that NOS-I is involved in the regulation of impulsive personality traits and support the notion that the NOS1 gene takes ..
  51. Parhad S, Jaiswal D, Ray K, Mazumdar S. The protein inhibitor of nNOS (PIN/DLC1/LC8) binding does not inhibit the NADPH-dependent heme reduction in nNOS, a key step in NO synthesis. Biochem Biophys Res Commun. 2016;472:189-93 pubmed publisher
    The neuronal nitric oxide synthase (nNOS) is an essential enzyme involved in the synthesis of nitric oxide (NO), a potent neurotransmitter...
  52. Rosa S, Judas F, Lopes M, Mendes A. Nitric oxide synthase isoforms and NF-kappaB activity in normal and osteoarthritic human chondrocytes: regulation by inducible nitric oxide. Nitric Oxide. 2008;19:276-83 pubmed publisher
    ..regulation of NF-kappaB activity in human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible (iNOS) NO synthase isoforms and the basal NF-kappaB activity in normal and osteoarthritic (OA) human ..
  53. Langbein H, Brunssen C, Hofmann A, Cimalla P, Brux M, Bornstein S, et al. NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice. Eur Heart J. 2016;37:1753-61 pubmed publisher
    ..In this setting, loss of Nox4-derived H2O2 production could be partially compensated for by nNOS upregulation...
  54. Gorska M, Zmijewski M, Kuban Jankowska A, Wnuk M, Rzeszutek I, Wozniak M. Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line. Mol Neurobiol. 2016;53:5030-40 pubmed publisher
    ..Thus, we are postulating that naturally occurring 2-methoxyestradiol may be considered a physiological modulator of neuron survival. ..
  55. Nagy Grócz G, Tar L, Bohár Z, Fejes Szabó A, Laborc K, Spekker E, et al. The modulatory effect of anandamide on nitroglycerin-induced sensitization in the trigeminal system of the rat. Cephalalgia. 2016;36:849-61 pubmed publisher
    ..NTG-induced expression of transient receptor potential vanilloid type 1 (TRPV1), neuronal nitric oxide synthase (nNOS), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and kynurenine aminotransferase-II (KAT-II) in the ..
  56. Wang J, Jin L, Zhu Y, Zhou X, Yu R, Gao S. Research progress in NOS1AP in neurological and psychiatric diseases. Brain Res Bull. 2016;125:99-105 pubmed publisher
    ..The review will promote the further investigation of NOS1AP in brain disorders and the development of drugs targeting the NOS1AP PTB domain or PDZ-binding motif in the future. ..
  57. Texereau J, Marullo S, Hubert D, Coste J, Dusser D, Dall Ava Santucci J, et al. Nitric oxide synthase 1 as a potential modifier gene of decline in lung function in patients with cystic fibrosis. Thorax. 2004;59:156-8 pubmed
    ..There was no confounding effect of age, chronic bacterial colonisation of the airway, or CFTR genotype. These data suggest a possible link between the NOS1 gene locus and the rate of decline in lung function in patients with CF. ..
  58. Zhu X, Dong J, Han B, Huang R, Zhang A, Xia Z, et al. Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior. Front Behav Neurosci. 2017;11:203 pubmed publisher
    ..we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling-induced cognitive impairment and depressive-like behavior...
  59. Li J, Han Z, Cao B, Cai C, Lin Y, Li F, et al. Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval. Biochem Biophys Res Commun. 2017;493:862-868 pubmed publisher
    ..The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we ..
  60. Krzyaniak M, Cruce A, Vennam P, Lockart M, Berka V, Tsai A, et al. The tetrahydrobiopterin radical interacting with high- and low-spin heme in neuronal nitric oxide synthase - A new indicator of the extent of NOS coupling. Free Radic Biol Med. 2016;101:367-377 pubmed publisher
    ..trapped during the single-turnover reaction of the neuronal ferrous nitric oxide synthase oxygenase domain (Fe(II)nNOSOX) show four EPR spectra of free radicals...
  61. Lau K, Grange R, Isotani E, Sarelius I, Kamm K, Huang P, et al. nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle. Physiol Genomics. 2000;2:21-7 pubmed
    Nitric oxide (NO) from Ca(2+)-dependent neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers may modulate vascular tone by a cGMP-dependent pathway similar to NO derived from NOS in endothelial cells (eNOS)...
  62. Vicente D, Montó F, Oliver E, Buendía F, Rueda J, Aguero J, et al. Myocardial and lymphocytic expression of eNOS and nNOS before and after heart transplantation: relationship to clinical status. Life Sci. 2013;93:108-15 pubmed publisher
    ..Expression of constitutive NOS isoforms in heart exhibits wide variability in HF patients, but this variability was not related to aetiology,..
  63. Kuhn M, Haaker J, Glotzbach Schoon E, Schümann D, Andreatta M, Mechias M, et al. Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes. Soc Cogn Affect Neurosci. 2016;11:803-12 pubmed publisher
    ..pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning ..
  64. Reif A. Is NOS1 a genetic link between RLS and ADHD?. J Psychiatr Res. 2010;44:60-1 pubmed publisher
  65. Shi Z, Zhu L, Li T, Tang X, Xiang Y, Han X, et al. Neuroprotective Mechanisms of Lycium barbarum Polysaccharides Against Ischemic Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways. Front Cell Neurosci. 2017;11:288 pubmed publisher
    ..we found that LBP antagonized increase in expression of major proteins in the NR2B signal pathway including NR2B, nNOS, Bcl-2-associated death promoter (BAD), cytochrome C (cytC) and cleaved caspase-3, and also reduced ROS level, ..
  66. Martinez B, Barrios K, Vergara C, Mercado D, Jimenez S, Gusmao L, et al. A NOS1 gene polymorphism associated with asthma and specific immunoglobulin E response to mite allergens in a Colombian population. Int Arch Allergy Immunol. 2007;144:105-13 pubmed
    ..pteronyssinus (p(c) < 0.0001). We found no association of the C5266T SNP and asthma or IgE levels. NOS1 exon 29 CA-repeat may be a risk factor for asthma susceptibility and mite specific IgE response in a Colombian population. ..
  67. Gao S, Qi X, Zhao J, Balesar R, Bao A, Swaab D. Decreased NOS1 expression in the anterior cingulate cortex in depression. Cereb Cortex. 2013;23:2956-64 pubmed publisher
    ..We aimed to determine the NO content in the cerebrospinal fluid (CSF) and the expression of NO synthase (NOS) isoforms, that is, NOS1, NOS2, and NOS3 in the ACC in depression...
  68. Cheng J, Valdivia C, Vaidyanathan R, Balijepalli R, Ackerman M, Makielski J. Caveolin-3 suppresses late sodium current by inhibiting nNOS-dependent S-nitrosylation of SCN5A. J Mol Cell Cardiol. 2013;61:102-10 pubmed publisher
    ..This increase was reversed by the neural nitric oxide synthase (nNOS) inhibitor L-NMMA...
  69. Frick L, Rapanelli M, Jindachomthong K, Grant P, Leckman J, Swedo S, et al. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behav Immun. 2018;69:304-311 pubmed publisher
    ..There was no elevated binding to two different populations of GABAergic interneurons (PV and nNOS-positive), confirming the specificity of this phenomenon...
  70. Liu Y, Bai J, Xu X, Chen Z, Spicer L, Feng T. Effects of N-carbamylglutamate and l-arginine on gonadotrophin-releasing hormone (GnRH) gene expression and secretion in GT1-7 cells. Reprod Fertil Dev. 2017;: pubmed publisher
    ..GnRH, Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), neuronal nitric oxide synthase (nNOS) and estrogen receptor ? (ER?) genes. High concentrations of NCG (1.0mM) and ARG (4.0mM) inhibited (P<0...
  71. Balat A, Alasehirli B, Oguzkan S, Gungor M. Nitric oxide synthase gene polymorphisms in children with primary nocturnal enuresis: a preliminary study. Ren Fail. 2007;29:79-83 pubmed
    ..This study aimed to investigate endothelial (eNOS), and neuronal (nNOS) NO synthase gene polymorphisms in children with primary nocturnal enuresis (PNE)...
  72. King B, Haque S, Stoner M, Ellis Z, Kellum J. Inhibition of neural nitric oxide synthase attenuates the chloride secretory response to stroking in human jejunum. Surgery. 2003;134:255-9 pubmed
  73. Galimberti D, Venturelli E, Gatti A, Lovati C, Fenoglio C, Mariani C, et al. Association of neuronal nitric oxide synthase C276T polymorphism with Alzheimer's disease. J Neurol. 2005;252:985-6 pubmed
  74. Levecque C, Elbaz A, Clavel J, Richard F, Vidal J, Amouyel P, et al. Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study. Hum Mol Genet. 2003;12:79-86 pubmed
    ..Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD)...
  75. Mule F, Vannucchi M, Corsani L, Serio R, Faussone Pellegrini M. Myogenic NOS and endogenous NO production are defective in colon from dystrophic (mdx) mice. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1264-70 pubmed
    ..Immunohistochemistry revealed that the presence and distribution of neuronal (nNOS), endothelial, and inducible NOS isoforms in smooth muscle cells and neurons of colon from mdx mice were the same ..
  76. Scott W, Zhang F, Stajich J, Scott B, Stacy M, Vance J. Family-based case-control study of cigarette smoking and Parkinson disease. Neurology. 2005;64:442-7 pubmed
    ..Other studies reported that smoking modified the risk of PD due to polymorphisms in the MAO-B and nNOS genes. Thus, genetic studies of PD should consider confounding or interaction with smoking history as well...
  77. Taktakishvili O, Lin L, Vanderheyden A, Nashelsky M, Talman W. Nitroxidergic innervation of human cerebral arteries. Auton Neurosci. 2010;156:152-3 pubmed publisher
  78. Song Y, Zweier J, Xia Y. Heat-shock protein 90 augments neuronal nitric oxide synthase activity by enhancing Ca2+/calmodulin binding. Biochem J. 2001;355:357-60 pubmed
    Heat-shock protein 90 (hsp90) has been shown to facilitate neuronal NO synthase (nNOS, type 1) activity in vivo. But the direct effect of hsp90 on purified nNOS has not been determined yet...
  79. Silberberg G, Ben Shachar D, Navon R. Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1318-28 pubmed publisher
    ..Additionally, multiple links have been reported between the NO-producing enzyme, nitric oxide synthase (NOS) 1, and both schizophrenia and bipolar disorder (BPD)...
  80. Shang T, Kotamraju S, Kalivendi S, Hillard C, Kalyanaraman B. 1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide. J Biol Chem. 2004;279:19099-112 pubmed
    ..Depletion of BH(4) decreased the active, dimeric form of neuronal nitric-oxide synthase (nNOS). MPP(+)-mediated "uncoupling" of nNOS decreased *NO and increased superoxide formation...
  81. Fang M, Jaffrey S, Sawa A, Ye K, Luo X, Snyder S. Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron. 2000;28:183-93 pubmed
    ..NO signaling may be enhanced by adaptor proteins that couple neuronal NO synthase (nNOS) to specific target proteins...
  82. Fan J, Zhang Q, Li M, Tochio H, Yamazaki T, Shimizu M, et al. Protein inhibitor of neuronal nitric-oxide synthase, PIN, binds to a 17-amino acid residue fragment of the enzyme. J Biol Chem. 1998;273:33472-81 pubmed
    Neuronal nitric-oxide synthase (nNOS) is the primary nitric oxide (NO) regulator in neurons. The activity of the enzyme is inhibited by a protein inhibitor called PIN...
  83. Mohammad Jafari R, Ghahremani M, Rahimi N, Shadboorestan A, Rashidian A, Esmaeili J, et al. The anticonvulsant activity and cerebral protection of chronic lithium chloride via NMDA receptor/nitric oxide and phospho-ERK. Brain Res Bull. 2018;137:1-9 pubmed publisher
    ..seizure animal model and the interaction of NMDA receptor antagonist (MK-801) and neuronal nitric oxide synthase (nNOS) inhibitor (7-NI) with these neuroprotection has been studied...
  84. O Donoghue T, Morris D, Fahey C, Da Costa A, Foxe J, Hoerold D, et al. A NOS1 variant implicated in cognitive performance influences evoked neural responses during a high density EEG study of early visual perception. Hum Brain Mapp. 2012;33:1202-11 pubmed publisher
  85. Hall A, Antoniou H, Wang Y, Cheung A, Arbus A, Olson S, et al. Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem. 1994;269:33082-90 pubmed
    ..In summary, analysis of the human neuronal NO synthase locus reveals a complex genomic organization and mRNA diversity that is both allelic and structural. ..
  86. Bernstein H, Dobrowolny H, Keilhoff G, Steiner J. In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons. Metab Brain Dis. 2017;32:2143-2147 pubmed publisher
    ..By using double immunolabeling technique for OTC and neuronal nitric oxide synthase (nNOS) OTC protein expression was revealed in a small subset of nitrergic (nNOS) neurons...
  87. Cui H, Nishiguchi N, Yanagi M, Fukutake M, Mouri K, Kitamura N, et al. A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain. Schizophr Res. 2010;121:172-8 pubmed publisher
    ..018). When the analyses took gender into account, this significance was more significant for female. These findings provide further evidences that NOS1 is associated with a biological susceptibility gene to schizophrenia. ..
  88. Bender A, Demady D, Osawa Y. Ubiquitination of neuronal nitric-oxide synthase in vitro and in vivo. J Biol Chem. 2000;275:17407-11 pubmed
    It is established that suicide inactivation of neuronal nitric-oxide synthase (nNOS) with guanidine compounds, or inhibition of the hsp90-based chaperone system with geldanamycin, leads to the enhanced proteolytic degradation of nNOS...