Affinage

NOS1

Nitric oxide synthase 1 · UniProt P29475

Round 2 corrected
Length
1434 aa
Mass
161.0 kDa
Annotated
2026-04-29
130 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOS1 (neuronal nitric oxide synthase) is a calmodulin- and Ca²⁺-dependent oxidoreductase that converts L-arginine to nitric oxide and L-citrulline using FAD, FMN, and NADPH as cofactors, functioning as an obligate homodimer whose activity is regulated by multisite serine phosphorylation (PKA, PKC, CaM kinase, AMPK), O-GlcNAcylation, BH4 availability, and caveolin-mediated tonic inhibition (PMID:1689048, PMID:1375933, PMID:22798524, PMID:28238085). An N-terminal PDZ domain governs subcellular targeting: interaction with PSD-95 couples NOS1 to NMDA receptor complexes at glutamatergic synapses to drive NO→sGC→cGMP signaling in auditory processing, fear extinction, and excitotoxic neuronal death; interaction with α1-syntrophin anchors NOS1 to the dystrophin–sarcoglycan complex at the skeletal-muscle sarcolemma, where it provides cGMP-mediated vasomodulation essential for fatigue resistance and whose loss is a shared feature of Duchenne muscular dystrophy and limb-girdle myopathies; and a syntrophin-scaffolded NOS1–PMCA4b–SCN5A macromolecular complex in cardiomyocytes regulates cardiac sodium current via S-nitrosylation of SCN5A (PMID:8625413, PMID:10221915, PMID:7545544, PMID:18953332, PMID:18591664, PMID:30530507). The competing adaptor CAPON redirects NOS1 signaling away from PSD-95 toward Dexras1 activation and modulates antidepressant responses in dentate gyrus (PMID:9459447, PMID:11086993, PMID:35664081). Heterozygous loss-of-function NOS1 mutations cause congenital hypogonadotropic hypogonadism with anosmia, hearing loss, and intellectual disability, phenotypes rescuable by inhaled NO during minipuberty (PMID:36197968).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Identification of NOS1 as a discrete enzyme resolved how neurons produce nitric oxide: a single 150-kDa polypeptide requires calmodulin, Ca²⁺, and NADPH to catalyze L-arginine→NO+L-citrulline.

    Evidence Protein purification to homogeneity from rat cerebellum with enzymatic assay

    PMID:1689048

    Open questions at the time
    • Cofactor stoichiometry and domain architecture not yet defined
    • Oligomeric state unknown
  2. 1992 High

    Defining NOS1 as a flavoprotein subject to inhibitory phosphorylation established that its activity is tonically regulated by kinase signaling, not simply by Ca²⁺/calmodulin binding.

    Evidence In vitro phosphorylation by PKA/PKC/CaM kinase, fluorescence spectroscopy revealing 1:1 FMN:FAD stoichiometry, PKC-dependent activity reduction in transfected cells

    PMID:1375933

    Open questions at the time
    • Phosphorylation sites not mapped to specific residues
    • In vivo relevance of phosphoregulation not tested
  3. 1995 High

    Discovery that NOS1 is anchored to the sarcolemma via dystrophin and is selectively lost in DMD/mdx muscle established that scaffold-dependent localization—not just expression—determines NOS1 function in disease.

    Evidence Immunofluorescence and subcellular fractionation in mdx mice and DMD patient biopsies

    PMID:7545544

    Open questions at the time
    • Direct binding domain not mapped
    • Functional consequence of sarcolemmal NOS1 loss for muscle contractility not tested
  4. 1996 High

    Identification of the NOS1 PDZ domain as a versatile protein–protein interaction module that binds PSD-95 (brain) and α1-syntrophin (muscle) unified the mechanism of tissue-specific NOS1 targeting.

    Evidence Co-immunoprecipitation from cerebellum, yeast two-hybrid, PDZ-deletion mutant mice lacking PSD-95/sarcolemmal association

    PMID:8625413

    Open questions at the time
    • Structural basis of PDZ–PDZ recognition not yet resolved
    • Whether other PDZ partners exist unknown
  5. 1998 High

    CAPON was identified as a brain-enriched adaptor that competes with PSD-95 for the NOS1 PDZ domain, revealing that NOS1 signaling specificity is determined by mutually exclusive adaptor binding rather than by enzyme activity alone.

    Evidence Yeast two-hybrid, co-immunoprecipitation, overexpression displacing PSD-95–NOS1 complexes

    PMID:9459447

    Open questions at the time
    • Physiological contexts governing CAPON vs PSD-95 selection unclear
    • Downstream signaling of CAPON-bound NOS1 undefined
  6. 1999 High

    Structural and biochemical studies resolved two key architectural features: (1) PSD-95 PDZ2 recognizes an internal β-finger of NOS1, enabling ternary NMDAR–PSD-95–NOS1 complex formation; (2) the NOS1–syntrophin PDZ–PDZ interaction uses a non-canonical head-to-tail docking mode.

    Evidence Crystal/NMR structure of NOS1 PDZ–syntrophin PDZ complex; in vitro reconstitution of ternary NMDAR complex

    PMID:10221915 PMID:10488080

    Open questions at the time
    • Full-length NOS1 structure unavailable
    • Whether ternary complex forms stoichiometrically in vivo not quantified
  7. 1999 High

    NOS1 localization to cardiac sarcoplasmic reticulum, where it generates Ca²⁺-dependent NO and inhibits SERCA-mediated Ca²⁺ uptake, established a cardiac-specific NOS1 function distinct from its neuronal and skeletal-muscle roles.

    Evidence EPR spin-trapping of NO, immunoelectron microscopy, Ca²⁺ uptake assay, confirmed absent in nNOS-KO hearts

    PMID:9892689

    Open questions at the time
    • Molecular anchor for SR-localized NOS1 unknown
    • Downstream effectors (PKG, S-nitrosylation) not dissected
  8. 2000 High

    The CAPON→Dexras1 ternary complex demonstrated that CAPON redirects NOS1-generated NO to activate a specific Ras-family GTPase, establishing the first defined signaling output of the NOS1–CAPON pathway.

    Evidence Co-immunoprecipitation, G-protein activation in cortical neurons, Dexras1 activation abolished in nNOS-KO mice

    PMID:11086993

    Open questions at the time
    • Downstream targets of activated Dexras1 unclear
    • Whether CAPON–Dexras1 axis operates in non-neuronal tissues unknown
  9. 2002 High

    Demonstrating that the complete sarcoglycan–sarcospan complex is required for NOS1 sarcolemmal retention extended the dystrophin-anchoring model and explained NOS1 loss in limb-girdle muscular dystrophies.

    Evidence Immunofluorescence and Western blot in α-, β-, δ-, γ-sarcoglycan-KO animals and LGMD patient biopsies

    PMID:12409321

    Open questions at the time
    • Whether sarcoglycan directly contacts NOS1 or acts indirectly via syntrophin conformation unknown
  10. 2008 High

    Two key functional consequences of NOS1 localization were defined: (1) sarcolemmal NOS1-derived cGMP provides vasomodulation essential for fatigue resistance in exercising muscle, and (2) α1-syntrophin scaffolds NOS1 with PMCA4b and SCN5A in cardiomyocytes, where NOS1-mediated S-nitrosylation of SCN5A regulates cardiac sodium current.

    Evidence nNOS-KO exercise studies with PDE5 inhibitor rescue and human biopsy; GST pull-down, electrophysiology, and S-nitrosylation assays in the cardiac SNTA1-A390V mutant system

    PMID:18591664 PMID:18953332

    Open questions at the time
    • Identity of all NOS1 S-nitrosylation substrates in cardiomyocytes not catalogued
    • Whether sarcolemmal NOS1 loss is cause or consequence of early myopathic changes debated
  11. 2012 High

    BH4 (via GCH1) was identified as a rate-limiting cofactor for constitutive cardiac NOS1 activity, and FMRP was shown to control NOS1 translation in developing human neocortex via species-specific mRNA motifs, adding cofactor availability and translational control to the regulatory repertoire.

    Evidence GCH1-transgenic mice with NOS1 inhibitor rescue and cardiac functional assays; RNA–protein interaction and human FXS post-mortem brain analysis

    PMID:22579290 PMID:22798524

    Open questions at the time
    • Whether BH4 also limits NOS1 in skeletal muscle or neurons not addressed
    • FMRP regulation of NOS1 restricted to human; mouse relevance absent
  12. 2013 High

    NOS1AP (CAPON) was shown to recruit MKK3/p38MAPK to NOS1, linking NMDA-driven NO production to excitotoxic cell death; disrupting this interaction with a competing peptide doubled surviving tissue in neonatal hypoxia-ischemia.

    Evidence Co-IP, siRNA, cell-permeable PDZ-competing peptides, p38MAPK assays, and in vivo neonatal rat HI model

    PMID:23658158

    Open questions at the time
    • Whether NOS1AP-p38MAPK pathway operates independently of NO catalytic activity not fully dissected
    • Long-term outcome of competing-peptide neuroprotection not assessed
  13. 2019 High

    Macula densa NOS1 was placed downstream of SGLT1 glucose sensing to blunt tubuloglomerular feedback: conditional macula densa NOS1 knockout abolished glucose-induced NO generation and hyperfiltration, establishing a kidney-specific NOS1 signaling axis.

    Evidence Macula densa-specific NOS1 conditional KO, micropuncture, SGLT1 inhibitor, NO imaging

    PMID:30867247

    Open questions at the time
    • Phosphorylation of NOS1 Ser1417 by a specific kinase downstream of SGLT1 not identified
    • Whether this pathway contributes to diabetic nephropathy chronically untested
  14. 2021 High

    NOS1 circuit-level roles were expanded: insular cortex NOS1-expressing glutamatergic neurons drive conditioned overconsumption via projections to the central amygdala, and NOS1AP variants that reduce NOS1 expression in hiPSC-cardiomyocytes mechanistically link NOS1 dysfunction to arrhythmia susceptibility in LQT1.

    Evidence Intersectional optogenetics/chemogenetics with behavioral assays; hiPSC-CM electrophysiology and NOS1 inhibitor pharmacology

    PMID:32061134 PMID:33761312

    Open questions at the time
    • Whether NOS1 neuron identity is marker-defined or functionally exclusive unknown
    • NOS1AP variant effect on NOS1 protein stability vs. transcription not resolved
  15. 2022 High

    Human genetic evidence established NOS1 as a disease gene: heterozygous loss-of-function mutations cause hypogonadotropic hypogonadism with anosmia, hearing loss, and intellectual disability, with phenotypic rescue by inhaled NO during minipuberty in mice.

    Evidence WES of 341 probands, in vitro enzymatic assays of mutant NOS1, Nos1-deficient mouse phenotyping and inhaled NO rescue

    PMID:36197968

    Open questions at the time
    • Mechanism by which transient neonatal NO exposure produces lasting rescue unclear
    • Genotype–phenotype correlations across different NOS1 mutations not established
  16. 2022 Medium

    NOS1–CAPON dissociation in the dentate gyrus was shown to mediate fluoxetine's antidepressant effects via 5-HT1A receptor signaling, positioning the NOS1–CAPON interaction as a convergence node for serotonergic and glutamatergic regulation of mood circuits.

    Evidence Chronic stress models, Co-IP, 5-HT1AR agonism/antagonism, NOS1–CAPON competing peptides, dendritic spine and behavioral analyses

    PMID:35664081

    Open questions at the time
    • Whether NOS1 catalytic activity is required for the antidepressant effect or only the adaptor switch matters is unresolved
    • Replication in independent labs needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the full-length holoenzyme structure in complex with its PDZ partners, the complete catalog of NOS1 S-nitrosylation substrates across tissues, the kinase directly responsible for SGLT1-dependent Ser1417 phosphorylation, and the mechanism by which transient neonatal NO exposure permanently rescues neurodevelopmental phenotypes.
  • No high-resolution structure of full-length NOS1 with any scaffold partner
  • Systematic identification of tissue-specific S-nitrosylation targets lacking
  • Neonatal NO rescue mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0009975 cyclase activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-112316 Neuronal System 6 R-HSA-1430728 Metabolism 5 R-HSA-397014 Muscle contraction 3 R-HSA-382551 Transport of small molecules 2 R-HSA-1266738 Developmental Biology 1
Partners
CAV3NOS1APPMCA4BPSD93PSD95RASD1SCN5ASNTA1
Complex memberships
Dystrophin–sarcoglycan–syntrophin–NOS1 sarcolemmal complexNMDAR–PSD-95–NOS1 postsynaptic complexNOS1–CAPON–Dexras1 ternary complexSNTA1–NOS1–PMCA4b–SCN5A cardiac macromolecular complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 NOS1 (neuronal nitric oxide synthase) was purified to homogeneity from rat cerebellum as a single 150-kDa polypeptide that requires calmodulin, NADPH, and Ca2+ for activity, catalyzing conversion of L-arginine to nitric oxide and L-citrulline. Purification used a 2',5'-ADP affinity column eluted with NADPH. Protein purification (affinity chromatography), enzymatic assay Proceedings of the National Academy of Sciences of the United States of America High 1689048
1992 NOS1 is stoichiometrically phosphorylated by cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and calcium/calmodulin-dependent protein kinase at distinct serine sites. PKC activation in transfected cells reduced NOS1 activity ~77%. Purified NOS1 monomer contains one molar equivalent each of FMN and FAD, and is labeled by a photoaffinity calmodulin derivative. In vitro phosphorylation assays, fluorescence spectroscopy, photoaffinity labeling, transfected cell activity assays The Journal of biological chemistry High 1375933
1993 Human NOS1 cDNA was cloned and expressed; the deduced amino acid sequence shows ~93% identity to rat brain NOS1 and contains binding sites for FAD, FMN, NADPH, and calmodulin. Unexpectedly, NOS1 mRNA is more abundant in human skeletal muscle than in brain, and NOS1 protein and enzymatic activity were confirmed in human skeletal muscle by Western blot. cDNA cloning, heterologous expression (COS-1 cells), Western blot, enzymatic activity assay, Northern blot FEBS letters High 7678401
1994 The human NOS1 gene spans >160 kb of genomic DNA on chromosome 12, is encoded by 28 exons, with a major transcription start site 28 nt downstream of a TATA box. Alternative splicing produces cassette exon deletions including one that introduces a frameshift and premature stop codon. A microsatellite in exon 29 shows allelic variation. Restriction mapping, subcloning, DNA sequencing, primer extension, RNase protection assay The Journal of biological chemistry High 7528745
1995 NOS1 is localized to the sarcolemma of fast-twitch skeletal muscle fibers through direct association with dystrophin via an N-terminal GLGF (PDZ) motif. In mdx mice and Duchenne muscular dystrophy patients, NOS1 protein and catalytic activity are selectively lost from muscle membranes, demonstrating that dystrophin anchors NOS1 at the sarcolemma. Immunofluorescence, subcellular fractionation, Western blot, enzymatic activity assay in dystrophin-deficient muscle Cell High 7545544
1996 NOS1 contains an N-terminal PDZ domain that mediates direct interaction with PDZ domains of PSD-95 and PSD-93 (postsynaptic density proteins) in brain, and with alpha1-syntrophin (a dystrophin-associated protein) in skeletal muscle. A PSD-95/nNOS complex was co-immunoprecipitated from cerebellum. nNOS isoforms lacking the PDZ domain (nNOSδ/δ mutant mice) do not associate with PSD-95 or sarcolemma. Co-immunoprecipitation, yeast two-hybrid, PDZ domain mutagenesis, nNOS knockout mice Cell High 8625413
1996 A 10-kDa protein designated PIN (protein inhibitor of nNOS) was identified by yeast two-hybrid screening; PIN directly binds NOS1 and inhibits its activity by destabilizing the NOS1 dimer, a conformation required for enzymatic activity. Yeast two-hybrid, in vitro binding, NOS1 dimerization assays, enzymatic activity assays Science High 8864115
1997 NOS1 directly interacts with caveolin-3 in skeletal muscle; both proteins are co-immunoprecipitated from rat skeletal muscle. Synthetic peptides corresponding to two distinct membrane-proximal domains of caveolin-3 (residues 65-84 and 109-130) potently inhibit purified NOS1 catalytic activity in vitro, defining two caveolin scaffolding/inhibitory domains. Co-immunoprecipitation from native muscle, GST pull-down, synthetic peptide inhibition assays with purified recombinant NOS1 The Journal of biological chemistry High 9353265
1998 CAPON (carboxy-terminal PDZ ligand of nNOS) was identified as a novel NOS1-associated adaptor protein enriched in brain. CAPON interacts with the NOS1 PDZ domain through its C-terminus and competes with PSD-95 for binding to NOS1. Overexpression of CAPON disrupts PSD-95/nNOS complexes in transfected cells, suggesting CAPON regulates NOS1 localization and its association with NMDA receptor complexes. Yeast two-hybrid, co-immunoprecipitation, immunohistochemistry, transfection/overexpression Neuron High 9459447
1998 NOS1 is a costameric enzyme in rat skeletal muscle, co-localizing with dystrophin, beta-dystroglycan, alpha/beta/gamma-sarcoglycan, beta1-integrin, vinculin, paxillin, and caveolin-3 at costameres, as shown by catalytic histochemistry and immunohistochemistry. NADPH-diaphorase catalytic histochemistry, immunohistochemistry with co-localization Acta histochemica Medium 9842423
1999 PSD-95 assembles a ternary complex with NOS1 and NMDA receptor subunits via PDZ domain interactions. NOS1 is recruited through a novel PDZ-PDZ interaction in which PSD-95 PDZ2 recognizes an internal pseudo-peptide motif adjacent to the NOS1 PDZ domain, leaving the NOS1 PDZ peptide-binding groove free to simultaneously bind additional C-terminal PDZ ligands (bivalent interaction). In vitro binding assays, co-immunoprecipitation, structural/biochemical characterization of PDZ interactions The Journal of biological chemistry High 10488080
1999 Crystal/NMR structural analysis of the NOS1 PDZ–syntrophin PDZ complex revealed an unusual head-to-tail linear arrangement where the NOS1 beta-hairpin 'finger' docks into the syntrophin peptide-binding groove, mimicking a peptide ligand without requiring a free carboxyl terminus. This established a non-canonical mode of PDZ-PDZ heterodimerization. X-ray crystallography / structural analysis with biochemical validation Science High 10221915
1999 A neuronal-type NOS1 isoform is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles. SR-associated NOS1 generates endogenous NO (detected by EPR spin-trapping) in a Ca2+-dependent manner and inhibits SR Ca2+ uptake by Ca2+-ATPase. Immunoelectron microscopy confirmed SR localization; the SR NOS1 (~160 kDa) is larger than brain NOS1 (~155 kDa), and NOS1 immunoreactivity was absent in cardiac SR from nNOS knockout mice. L-arginine to L-citrulline conversion assay, EPR spin-trapping, immunoelectron microscopy, confocal immunofluorescence, Western blot, Ca2+ uptake assay, nNOS knockout mice Proceedings of the National Academy of Sciences of the United States of America High 9892689
1999 NOS1 and caveolin-1 (in endothelium) and NOS1 and caveolin-3 (in skeletal muscle sarcolemma) are co-distributed throughout the systemic vasculature and skeletal muscle in vivo, consistent with physical regulatory interactions between these proteins in intact tissues. Immunohistochemistry of intact hamster tissues (vasculature, muscle) The American journal of physiology Medium 10484439
2000 CAPON links NOS1 to Dexras1, a brain-enriched Ras-family small G protein. NOS1, CAPON, and Dexras1 form a ternary complex; NMDA receptor-stimulated NO synthesis activates Dexras1 in cortical neurons. In nNOS-/- mice, Dexras1 activation is selectively reduced without affecting other Ras family members, establishing NOS1-derived NO as a physiologic activator of Dexras1 via the CAPON adaptor. Co-immunoprecipitation, yeast two-hybrid, G protein activation assays in neurons, nNOS knockout mice Neuron High 11086993
2000 NOS1 (nNOSμ) in human skeletal muscle is phosphorylated at Ser1451 approximately 5.5-fold following a 30-s sprint exercise, coincident with AMPK-alpha1 and -alpha2 activation and ACC Ser79 phosphorylation, suggesting AMPK-mediated phosphorylation of NOS1 during metabolic stress. Phospho-specific immunoblotting of human muscle biopsies, AMPK activity assays American journal of physiology. Endocrinology and metabolism Medium 11052978
2000 NOS1 in human neuroblastoma cells is upregulated by oxidative stress (serum deprivation) and the resulting NO/cGMP production mediates neuroprotection through: (1) S-nitrosylation and inhibition of caspase-3, (2) upregulation of anti-apoptotic Bcl-2, and (3) downregulation of pro-apoptotic p66shc. Pharmacological inhibition of NOS1 or guanylyl cyclase abolished these protective effects. Pharmacological inhibition of NOS1 and guanylyl cyclase, cGMP measurement, caspase activity assay, Western blot for Bcl-2 and p66shc FASEB journal Medium 11023998
2000 NOS1 is functionally expressed in bovine vascular smooth muscle (VSM) stripped of endothelium. Serotonin stimulation increases cGMP and HSP20 phosphorylation in a NOS-dependent manner. NOS1 immunoreactivity was found in arterial smooth muscle media; a selective NOS1 inhibitor (7-nitroindazole) reduced L-arginine to L-citrulline conversion by 99% and augmented KCl-induced contractions. Immunohistochemistry, Western blot, L-arginine conversion assay, cGMP measurement, pharmacological inhibition American journal of physiology. Heart and circulatory physiology Medium 10710369
2002 Loss of the sarcoglycan-sarcospan complex in sarcoglycan-deficient animals and LGMD patients causes dramatic reduction of NOS1 at the sarcolemma, even when dystrophin and syntrophin are present. Expression of three out of four sarcoglycans is insufficient to maintain sarcolemmal NOS1, indicating that the complete sarcoglycan complex is required for NOS1 sarcolemmal localization. Western blot, immunofluorescence in sarcoglycan knockout animals and patient biopsies FASEB journal High 12409321
2003 NMDA receptor activation in rat cortical neurons decreases NOS1 phosphorylation (increasing its activity) via a mechanism dependent on calcineurin and PP1/PP2A phosphatases. Calcineurin inhibition blocked NMDA-induced nitrotyrosine accumulation and TUNEL positivity, linking NOS1 dephosphorylation to neuronal death by excitotoxicity. Quantitative digital microscopy, phospho-immunoblotting, NMDA receptor antagonists and phosphatase inhibitors, TUNEL assay Neurobiology of aging Medium 14643384
2008 Alpha1-syntrophin links NOS1 to PMCA4b, which tonically inhibits NOS1 activity in a complex that also contains the cardiac sodium channel SCN5A. A missense mutation (A390V) in SNTA1 disrupts PMCA4b binding, releasing NOS1 inhibition, causing S-nitrosylation of SCN5A and increased peak and late sodium current, establishing the nNOS-SNTA1-SCN5A macromolecular complex as a key regulator of cardiac sodium current. GST pull-down, co-immunoprecipitation, heterologous expression electrophysiology, S-nitrosylation assay, primary cardiomyocyte patch-clamp Proceedings of the National Academy of Sciences of the United States of America High 18591664
2008 Sarcolemma-localized NOS1 signaling in skeletal muscle is required to maintain activity after mild exercise, specifically by providing cGMP-mediated vasomodulation in vessels supplying active muscle. nNOS-null mice show exaggerated fatigue without muscle pathology or loss of specific force; pharmacological PDE5 inhibition (increasing cGMP) relieved prolonged inactivity in nNOS-mislocalization mouse models. Sarcolemmal nNOS was reduced in biopsies from diverse human myopathies. nNOS knockout and mislocalization mouse models, in vivo exercise studies, PDE5 inhibitor pharmacology, human muscle biopsy immunostaining Nature High 18953332
2008 Renal medullary ETB receptor stimulation induces diuresis and natriuresis specifically through a NOS1→cGMP→PKG pathway. The NOS1-selective inhibitor NPA suppressed ETB agonist (S6c)-induced increases in urine flow, urinary sodium excretion, and medullary cGMP; PKG inhibition produced similar effects. These responses were absent in ETB receptor-deficient rats. In vivo renal microperfusion in anesthetized rats, NOS1-selective inhibitor (N(G)-propyl-L-arginine), PKG inhibitors, ETB-deficient rat model, cGMP measurement American journal of physiology. Renal physiology High 18305094
2012 FMRP (fragile X mental retardation protein) regulates translation of NOS1 in the developing human neocortex via interactions with coding-region binding motifs present in human NOS1 mRNA but absent from mouse Nos1 mRNA. NOS1 protein is transiently co-expressed with FMRP during early synaptogenesis in layer- and region-specific pyramidal neurons. NOS1 protein is severely reduced in developing human FXS brains but not in FMRP-deficient mice. Immunohistochemistry, Western blot, RNA-protein interaction assays, human FXS post-mortem brain analysis Cell High 22579290
2012 Myocardial GCH1 transgenic overexpression increases BH4 levels and NOS1 activity, accelerating cardiomyocyte relaxation and SR Ca2+ decay. The effects on PLB Ser16 phosphorylation, ICa density, [Ca2+]i decay, and myocardial relaxation were abolished by NOS1 inhibition but not by xanthine oxidoreductase inhibition, establishing BH4/GCH1 as a limiting factor for constitutive NOS1 activity in the healthy heart and NOS1 as the downstream effector of BH4-dependent cardiac relaxation. Transgenic mouse model (mGCH1-Tg), isolated heart and myocyte functional assays, NOS1 inhibition, Ca2+ imaging, phospho-immunoblotting, RyR2 S-nitrosylation assay Circulation research High 22798524
2013 NOS1AP (CAPON) interacts with MKK3 (a p38MAPK-activating kinase). Excitotoxic stimulation recruits NOS1AP to NOS1 in rat cortical neurons. Competing with the NOS1:NOS1AP interaction (via a cell-permeable peptide targeting the unique NOS1 PDZ domain) or NOS1AP siRNA knockdown reduces NMDA-induced p38MAPK activation and neuronal death. In vivo, the competing peptide doubled surviving tissue in a neonatal rat hypoxia-ischemia model. Co-immunoprecipitation, siRNA knockdown, cell-permeable competing peptides, p38MAPK activity assays, in vivo rat HI model with tissue survival quantification The Journal of neuroscience High 23658158
2017 NOS1 S-nitrosylates PTEN in nasopharyngeal carcinoma cells, promoting AKT/mTOR signaling activation and inhibiting excessive autophagy to promote cancer cell survival. Direct interaction between NOS1 and PTEN was detected. In vivo, NOS1 inhibition activated autophagy in xenograft tumors. NOS1 siRNA, pharmacological inhibition, S-nitrosylation assay, AKT/mTOR western blot, autophagy assays, co-immunoprecipitation, xenograft mouse model Cell death discovery Medium 28243469
2017 O-GlcNAc transferase interacts with NOS1 to modify it by O-linked-β-N-acetylglucosamine (O-GlcNAcylation). This modification increases during glutamate-induced excitotoxicity. Eliminating NOS1 O-GlcNAcylation protects neurons from apoptosis by decreasing formation of nNOS-PSD-95 complexes. Co-immunoprecipitation (NOS1–OGT interaction), O-GlcNAc immunoblot, genetic elimination of O-GlcNAcylation site, neuronal apoptosis assays Cellular and molecular neurobiology Medium 28238085
2018 NOS1 forms discrete membrane puncta complexes containing NMDA receptors, soluble guanylyl cyclase (sGC), and PSD-95 at glutamatergic synapses in all neurons of the central nucleus of the inferior colliculus. In vivo electrophysiology showed NMDA-enhanced sound-driven activity is completely abolished by NOS1 or sGC blockade, demonstrating that NMDA receptor modulation of auditory processing in this nucleus is entirely mediated through NOS1→NO→cGMP signaling. Immunohistochemistry, multi-labeling confocal microscopy, in vivo electrophysiology with pharmacological NOS1 and sGC blockade The Journal of neuroscience High 30530507
2018 Contextual fear extinction induces a shift from PSD-95–NOS1 to PSD-95–TrkB association in dorsal hippocampus. Disrupting PSD-95–NOS1 coupling in dorsal CA3 upregulates ERK phosphorylation and BDNF, enhances PSD-95–TrkB association, and promotes fear extinction. Blocking NMDA receptors in CA3 downregulates BDNF and impairs extinction, revealing opposing roles of NMDA receptor activation vs. PSD-95–NOS1 coupling in this circuit. Co-immunoprecipitation, Western blot, stereotaxic microinfusion of PDZ-competing peptides, behavioral fear extinction paradigm Scientific reports Medium 30143658
2018 Sarcolemmal loss of active NOS1 from skeletal muscle precedes myofiber atrophy during unloading and is induced by mitochondrial superoxide production. Displaced NOS1 activity in the sarcoplasm drives FoxO3 nuclear translocation to initiate atrophy; pharmacological inhibition of NOS1 in vivo before and during unloading prevented FoxO3 nuclear accumulation. NADPH-diaphorase histochemistry, immunofluorescence, NOS1 transcript/protein quantification, tropomyosin disulfide bond measurement (oxidant proxy), NOS1 inhibitor in vivo, FoxO3 nuclear localization assay in human and rat muscle The Journal of pathology Medium 30066461
2019 At the macula densa, SGLT1 senses luminal glucose and upregulates NOS1 expression and phosphorylation at Ser1417, increasing NOS1-derived NO production, which blunts the tubuloglomerular feedback (TGF) response and promotes glomerular hyperfiltration. Macula densa-specific NOS1 knockout mice showed no glucose-induced changes in NO generation, TGF, or GFR, establishing the SGLT1–NOS1 pathway as the mechanism of acute hyperglycemia-induced hyperfiltration. Macula densa-specific NOS1 conditional knockout, microperfusion, micropuncture, renal clearance (FITC-inulin), SGLT1 inhibitor (KGA-2727), NO fluorescence imaging, Western blot for NOS1 Ser1417 Journal of the American Society of Nephrology High 30867247
2021 Insular cortex NOS1-expressing glutamatergic neurons project to the central amygdala and are specifically active during feeding bouts. This circuit is necessary for conditioned (cue-driven) overconsumption but not homeostatic feeding; activation of insular cortex NOS1 neurons suppresses satiety signals in the central amygdala. Intersectional genetic viral vector approach, optogenetic activation, fiber photometry, chemogenetic circuit manipulation, behavioral assays (conditioned overconsumption) Cell metabolism High 33761312
2021 Myocardial BH4 (via GCH1 transgene or oral supplementation) prevents and reverses diabetic LV diastolic and systolic dysfunction through NOS1-mediated NO/sGC/PKG signaling that increases insulin-independent myocardial glucose uptake via GLUT-1. CRISPR/Cas9 knockout of NOS1 in mGCH1-Tg mice abolished the BH4-dependent protective effects, placing NOS1 as the essential effector. CRISPR/Cas9 NOS1 knockout in transgenic mice, echocardiography, Ca2+ imaging, glucose uptake assay, 31P-MRS, mitochondrial function assays Circulation research High 33494625
2021 NOS1AP SNPs (minor alleles rs16847548 and rs4657139) are associated with reduced NOS1 expression and NOS1-NOS1AP co-localization in hiPSC-derived cardiomyocytes from symptomatic LQT1 patients. Pharmacological NOS1 inhibition in guinea-pig cardiomyocytes prolongs APD, enhances ICaL and INaL, slows Ca2+ decay, and induces delayed afterdepolarizations, establishing NOS1 dysfunction as a mechanistic link between NOS1AP variants and arrhythmia susceptibility. hiPSC-CMs from genotyped LQT1 patients, guinea-pig cardiomyocyte LQT1 model, patch-clamp electrophysiology, action-potential clamp, Ca2+ imaging, NOS1 inhibitor pharmacology Cardiovascular research High 32061134
2022 Heterozygous loss-of-function mutations in NOS1 cause congenital hypogonadotropic hypogonadism with anosmia, hearing loss, and intellectual disability. NOS1 is transiently expressed by GnRH neurons in the nose of humans and mice; Nos1-deficient mice show dose-dependent defects in sexual maturation, olfaction, hearing, and cognition. Inhaled NO treatment during the minipuberty window rescued reproductive and behavioral phenotypes in Nos1-deficient mice. Whole-exome sequencing of 341 probands, in vitro nitrite/cGMP assays of mutant NOS1 proteins, Nos1-deficient mouse model, pharmacological inhibition during minipuberty, inhaled NO rescue Science translational medicine High 36197968
2022 NOS1 dissociation from CAPON in the dentate gyrus (DG) is required for the anxiolytic and antidepressant effects of fluoxetine. Chronic fluoxetine or 5-HT1A receptor agonism reduces nNOS-CAPON expression and coupling in DG; augmenting nNOS-CAPON binding neutralizes fluoxetine-induced spine density increases, BDNF, and ERK/CREB/synapsin phosphorylation, and abolishes behavioral effects. CAPON dissociation from NOS1 is downstream of 5-HT1A receptor activation. Chronic mild stress and corticosterone mouse models, co-immunoprecipitation, pharmacological 5-HT1AR agonism/antagonism, NOS1-CAPON competing peptides, dendritic spine analysis, behavioral assays (anxiety, depression) Theranostics Medium 35664081

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proceedings of the National Academy of Sciences of the United States of America 3169 1689048
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1996 Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell 1413 8625413
1993 Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proceedings of the National Academy of Sciences of the United States of America 828 7682706
1995 Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 826 7545544
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1992 Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proceedings of the National Academy of Sciences of the United States of America 648 1379716
1992 Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. The Journal of biological chemistry 526 1375933
1993 Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS letters 501 7678401
1998 Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 492 9657518
1999 PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. The Journal of biological chemistry 464 10488080
1999 Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science (New York, N.Y.) 449 10221915
1999 Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America 402 9892689
1996 PIN: an associated protein inhibitor of neuronal nitric oxide synthase. Science (New York, N.Y.) 393 8864115
1996 Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science (New York, N.Y.) 360 8943206
2005 Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. American journal of human genetics 327 16380905
2008 Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 310 18821565
1998 CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95. Neuron 307 9459447
1998 Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 305 9412493
1996 Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 278 8922396
2000 AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. American journal of physiology. Endocrinology and metabolism 275 11052978
2000 Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 272 11086993
1993 Expression of nitric-oxide synthase (NOS) in injured CNS neurons as shown by NADPH diaphorase histochemistry. Experimental neurology 247 7684000
1994 Structural organization of the human neuronal nitric oxide synthase gene (NOS1). The Journal of biological chemistry 246 7528745
2003 The DDAH/ADMA/NOS pathway. Atherosclerosis. Supplements 245 14664901
2019 Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS? International journal of molecular sciences 241 31382355
2008 Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proceedings of the National Academy of Sciences of the United States of America 241 18591664
2008 Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 240 18953332
2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. The Journal of infectious diseases 223 17703412
1997 Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. The Journal of biological chemistry 213 9353265
2010 Characterization of a nitric oxide synthase from the plant kingdom: NO generation from the green alga Ostreococcus tauri is light irradiance and growth phase dependent. The Plant cell 203 21119059
2006 A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function. Molecular psychiatry 179 16389274
2009 Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample. Molecular psychiatry 178 19844207
2018 Endothelial NOS: perspective and recent developments. British journal of pharmacology 140 30341769
2003 From molecules to mammals: what's NOS got to do with it? Acta physiologica Scandinavica 126 14510775
2003 Mitochondrial nitric oxide synthase is not eNOS, nNOS or iNOS. Free radical biology & medicine 112 14607521
2012 Species-dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell 111 22579290
1996 Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. Human reproduction (Oxford, England) 107 9021370
2002 Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia. Molecular psychiatry 102 12140778
1999 Codistribution of NOS and caveolin throughout peripheral vasculature and skeletal muscle of hamsters. The American journal of physiology 98 10484439
2015 Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. Genes, brain, and behavior 92 25612209
2007 Differences in inflammatory pain in nNOS-, iNOS- and eNOS-deficient mice. European journal of pain (London, England) 91 17395508
2021 A lysine-cysteine redox switch with an NOS bridge regulates enzyme function. Nature 83 33953398
2019 Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia. Journal of the American Society of Nephrology : JASN 82 30867247
2013 The nNOS-p38MAPK pathway is mediated by NOS1AP during neuronal death. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 23658158
1997 Interaction of PKC and NOS in signal transduction of microvascular hyperpermeability. The American journal of physiology 78 9374783
2000 Functional expression of NOS 1 in vascular smooth muscle. American journal of physiology. Heart and circulatory physiology 75 10710369
2000 Preconditioning regulation of bcl-2 and p66shc by human NOS1 enhances tolerance to oxidative stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 73 11023998
2002 Loss of sarcolemma nNOS in sarcoglycan-deficient muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 12409321
2008 Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome. Movement disorders : official journal of the Movement Disorder Society 66 18058820
2011 The PSD-95/nNOS complex: new drugs for depression? Pharmacology & therapeutics 65 22133842
2008 Renal medullary ETB receptors produce diuresis and natriuresis via NOS1. American journal of physiology. Renal physiology 64 18305094
2004 Expression of nNOS and soluble guanylate cyclase in schizophrenic brain. Neuroreport 62 15094474
1998 Genetic analysis of NOS isoforms using nNOS and eNOS knockout animals. Progress in brain research 62 9932431
2006 Nitric oxide synthase (NOS) as therapeutic target for asthma and chronic obstructive pulmonary disease. Current drug targets 59 16787174
2003 Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis. American journal of physiology. Lung cellular and molecular physiology 58 14660484
2012 Decreased NOS1 expression in the anterior cingulate cortex in depression. Cerebral cortex (New York, N.Y. : 1991) 56 22989585
2003 NMDA receptor regulation of nNOS phosphorylation and induction of neuron death. Neurobiology of aging 55 14643384
2005 Expression of neuronal nitric oxide synthase (nNOS) and nitric-oxide-induced changes in cGMP in the urothelial layer of the guinea pig bladder. Cell and tissue research 52 15965654
1998 Role of macula densa NOS in tubuloglomerular feedback. Current opinion in nephrology and hypertension 51 9690045
2014 Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling. Frontiers in cellular neuroscience 50 25221472
2014 The role of nNOS and PGC-1α in skeletal muscle cells. Journal of cell science 49 25217629
2013 A scallop nitric oxide synthase (NOS) with structure similar to neuronal NOS and its involvement in the immune defense. PloS one 49 23922688
2017 Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus. The Journal of comparative neurology 46 28577305
1999 Neuronal expression of NOS-1 is required for host recovery from viral encephalitis. Virology 46 10366576
2021 Regulation of NOS expression in vascular diseases. Frontiers in bioscience (Landmark edition) 44 34027652
2011 nNOS regulation of skeletal muscle fatigue and exercise performance. Biophysical reviews 44 28510048
1998 NO generation and action during changes in salt intake: roles of nNOS and macula densa. The American journal of physiology 44 9608012
2014 Melanoma NOS1 expression promotes dysfunctional IFN signaling. The Journal of clinical investigation 41 24691438
2011 Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration. Journal of molecular medicine (Berlin, Germany) 40 22198001
2018 Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS. Blood advances 39 30194138
2012 NOS-2 signaling and cancer therapy. IUBMB life 39 22715033
2017 NOS1 S-nitrosylates PTEN and inhibits autophagy in nasopharyngeal carcinoma cells. Cell death discovery 38 28243469
1999 Neuronal NO synthase (NOS1) is a major candidate gene for asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 38 10641565
2012 Cardiomyocyte GTP cyclohydrolase 1 and tetrahydrobiopterin increase NOS1 activity and accelerate myocardial relaxation. Circulation research 37 22798524
2001 Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosis in fawn-hooded hypertensive rats. American journal of physiology. Renal physiology 37 11249862
2023 nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story. Neuroscience bulletin 36 37074530
2021 Top-down control of conditioned overconsumption is mediated by insular cortex Nos1 neurons. Cell metabolism 35 33761312
2005 The DDAH-ADMA-NOS pathway. Therapeutic drug monitoring 34 16404814
2018 Sarcolemmal loss of active nNOS (Nos1) is an oxidative stress-dependent, early event driving disuse atrophy. The Journal of pathology 33 30066461
2016 The TLR4-NOS1-AP1 signaling axis regulates macrophage polarization. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 33 28013342
2018 PSD-95-nNOS Coupling Regulates Contextual Fear Extinction in the Dorsal CA3. Scientific reports 32 30143658
2008 The protective effect of neuronal nitric oxide synthase (nNOS) against alcohol toxicity depends upon the NO-cGMP-PKG pathway and NF-kappaB. Neurotoxicology 32 18824032
2022 NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice. Science translational medicine 31 36197968
2009 Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 30 19365734
2022 Requirement of hippocampal DG nNOS-CAPON dissociation for the anxiolytic and antidepressant effects of fluoxetine. Theranostics 29 35664081
2002 Thioredoxin-related regulation of NO/NOS activities. Annals of the New York Academy of Sciences 29 12076971
2022 The expanding roles of neuronal nitric oxide synthase (NOS1). PeerJ 28 35821897
2019 Novel long-range inhibitory nNOS-expressing hippocampal cells. eLife 28 31609204
2008 Evidence for association between the 5' flank of the NOS1 gene and schizophrenia in the Chinese population. The international journal of neuropsychopharmacology 28 18544180
2014 Evidence for the contribution of NOS1 gene polymorphism (rs3782206) to prefrontal function in schizophrenia patients and healthy controls. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 27 25490993
2010 An inducible nitric oxide synthase (NOS) is expressed in hemocytes of the spiny lobster Panulirus argus: cloning, characterization and expression analysis. Fish & shellfish immunology 27 20580828
2006 Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain. BMC neuroscience 27 17184520
2018 Puncta of Neuronal Nitric Oxide Synthase (nNOS) Mediate NMDA Receptor Signaling in the Auditory Midbrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 30530507
2007 Increased longevity of hematopoiesis in continuous bone marrow cultures derived from NOS1 (nNOS, mtNOS) homozygous recombinant negative mice correlates with radioresistance of hematopoietic and marrow stromal cells. Experimental hematology 26 17198882
2018 Role of neuronal nitric oxide synthase (nNOS) in Duchenne and Becker muscular dystrophies - Still a possible treatment modality? Neuromuscular disorders : NMD 25 30352768
2008 Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst. Free radical biology & medicine 25 18675339
2021 NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis. Cardiovascular research 24 32061134
2021 Mechanisms of angiogenic incompetence in Hutchinson-Gilford progeria via downregulation of endothelial NOS. Aging cell 24 34086398
2019 Somatostatin+/nNOS+ neurons are involved in delta electroencephalogram activity and cortical-dependent recognition memory. Sleep 24 31328777
2020 Macrophage neuronal nitric oxide synthase (NOS1) controls the inflammatory response and foam cell formation in atherosclerosis. International immunopharmacology 23 32193098
2016 Role of ERK1/2 activation and nNOS uncoupling on endothelial dysfunction induced by lysophosphatidylcholine. Atherosclerosis 23 28235709
2005 NOS 1 is required for allergen-induced expression of NOS 2 in mice. International archives of allergy and immunology 23 16103686
2020 NOS1 expression promotes proliferation and invasion and enhances chemoresistance in ovarian cancer. Oncology letters 22 32218855
2020 Effects of selective inhibition of nNOS and iNOS on neuropathic pain in rats. Molecular and cellular neurosciences 22 32353527
2020 Leptin Contributes to Neuropathic Pain via Extrasynaptic NMDAR-nNOS Activation. Molecular neurobiology 22 33099751
2012 Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics. IUBMB life 22 22271455
2021 BH4 Increases nNOS Activity and Preserves Left Ventricular Function in Diabetes. Circulation research 21 33494625
2020 An autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through deregulated VEGFA, NOS1, and CTNNB1. Autophagy 21 32579471
2013 On the selectivity of neuronal NOS inhibitors. British journal of pharmacology 21 23072468
2011 The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals. NeuroImage 21 22227051
1998 Nitric oxide synthase I (NOS I) is a costameric enzyme in rat skeletal muscle. Acta histochemica 21 9842423
2022 Inhibition of interferon-gamma-stimulated melanoma progression by targeting neuronal nitric oxide synthase (nNOS). Scientific reports 20 35105915
2019 Interplay of Nitric Oxide Synthase (NOS) and SrrAB in Modulation of Staphylococcus aureus Metabolism and Virulence. Infection and immunity 20 30420450
2016 Transcriptional activation and translocation of ancient NOS during immune response. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 27402673
2002 The avian griseum tectale: cytoarchitecture, NOS expression and neurogenesis. Brain research bulletin 20 11922988
2018 NOS1 mediates AP1 nuclear translocation and inflammatory response. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 29605772
2018 NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells. Oncology letters 19 30675218
2017 O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. Cellular and molecular neurobiology 19 28238085
2016 The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca(2+)-NOS pathway. Scientific reports 19 27538454
2016 Human Ischemic Cardiomyopathy Shows Cardiac Nos1 Translocation and its Increased Levels are Related to Left Ventricular Performance. Scientific reports 18 27041589
2016 NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 18 27354091
2017 Expression dynamics of HSP90 and nitric oxide synthase (NOS) isoforms during heat stress acclimation in Tharparkar cattle. International journal of biometeorology 17 28265771
2009 No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population. Neuromolecular medicine 17 19513863
2021 GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation. International journal of molecular sciences 16 33435517
2020 Changes of nNOS expression in the tuberal hypothalamic nuclei during ageing. Nitric oxide : biology and chemistry 16 32283261
2015 On the role of NOS1 ex1f-VNTR in ADHD-allelic, subgroup, and meta-analysis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 16 26086921
2002 Differential diagnosis of salivary acinic cell carcinoma and adenocarcinoma (NOS). A comparison of (immuno-)histochemical markers. Pathology, research and practice 16 12608654
2001 Sepsis is associated with reciprocal expressional modifications of constitutive nitric oxide synthase (NOS) in human skeletal muscle: down-regulation of NOS1 and up-regulation of NOS3. Critical care medicine 16 11546971