Disease relevance of Nos1

• The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis [1].
• Thus, reduction of uveitis symptoms correlates with the inhibition of c-NOS [2].
• Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl(4)-induced cirrhotic rats with ascites [1].
• Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis [1].
• Our results show that the three NOS isoforms participate in increasing NO levels after transient ischemia and suggest a biphasic and differential regulation of the expression of constitutive NOS isoforms in the rat cerebral cortex [3].

Psychiatry related information on Nos1

• The effects of different COX and NOS inhibitors on the intestinal motor activity were tested. mRNA expression of COX-1 was not modified by inflammation, whereas mRNA expression of neuronal NOS was reduced in all indomethacin-treated rats [4].
• BACKGROUND: Although long-term alcohol consumption impairs both endothelial nitric oxide synthase (NOS) (eNOS)-dependent and neuronal NOS (nNOS)-dependent reactivity of cerebral arterioles in male rats, the influence of sex on alcohol consumption-induced impairment of NOS-dependent cerebral vasodilation has not been examined [5].
• Our results represent the first evidence that amyloid fragments impair constitutive NOS activity in cell-free and cellular systems, providing a possible molecular mechanism for the onset and/or maintenance of Alzheimer's disease [6].
• Intrathecal injection of nNOS antisense oligonucleotides (nNOS-AS) inhibited the increase of Fos protein and NMDA(1A)R mRNA expression in the rat spinal cord during morphine withdrawal and decreased the scores of morphine withdrawal symptoms [7].

High impact information on Nos1

• These results reveal a novel human nNOS promoter that confers the ability to rapidly upregulate nNOS expression in response to hypoxia with a functionally significant effect on vascular smooth muscle contraction [8].
• Expression of nNOS in each liver cell type, whether from normal or injured liver, caused increased NO production and inhibited endothelin-1-induced contractility of perisinusoidal stellate cells [9].
• Recombinant adenovirus (Ad) carrying the neuronal NOS gene (nNOS) targeted liver sinusoidal endothelial cells, stellate cells, and hepatocytes more efficiently than the corresponding cells in cirrhotic livers, but transduction rates were substantial even in cirrhotic animals [9].
• We also investigated if stimulation of the nicotinic receptor increases neuronal NOS (nNOS) expression in cultured gastric myenteric ganglia [10].
• We concluded that activation of the nicotinic receptor stimulates a Ca2+-dependent protein kinase C pathway, which in turn, upregulates nNOS mRNA expression and nNOS synthesis in the gastric myenteric plexus [10].

Chemical compound and disease context of Nos1

• Pretreatment with 3-bromo-7-nitroindazole (7-NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27+/-0.17 mm3 [mean+/-SEM], p < 0.05) compared with that of control (2.52+/-0.35 mm3) [11].
• Three types of NOS must be related to different stages of ischemic brain damage. nNOS may be neurotoxic in ischemia in the early phase, like iNOS in the late phase [12].
• We also assessed the contribution of the neuronal (nNOS), the endothelial (eNOS), and the inducible (iNOS) isoforms of nitric oxide synthase (NOS) to tyrosine nitration in skeletal muscles both under normal conditions and in response to severe sepsis [13].
• These findings indicate that the early-phase isoflurane-induced hypotension may involve nNOS as well as eNOS [14].
• This hyperalgesia was dose-dependently and reversibly attenuated by intrathecal administration of the nonselective NO* synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (100-800 nmol) as well as by the selective neuronal NOS inhibitor ARL 17477 (30-600 nmol) [15].

Biological context of Nos1

• To elucidate the mechanism of nNOS regulation by caveolin, we examined the effects of a caveolin-1 scaffolding domain peptide (CaV1p1; residues (82-101)) on the catalytic activities of wild-type and mutant nNOSs [16].
• Denervated muscle displayed distinct downregulation of nNOS with preserved expression of dystrophin [17].
• Increased counteracting effect of eNOS and nNOS on an alpha1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats [18].
• This model gives rise to the hypothesis that the upregulation of the eNOS maintains the physiological production of NO, while the iNOS is silenced and the nNOS remains unchanged [19].
• Nitric oxide produced via neuronal NOS may impair vasodilatation in septic rat skeletal muscle [20].

Anatomical context of Nos1

• This was addressed by measuring Nos1, Nos2, and Nos3 mRNA in the kidney, adrenal gland, heart, and hypothalamus of 16 ACTH-treated and 16 vehicle-treated rats as well as in 10 corticosterone-treated and 10 control rats [21].
• CONCLUSION/INTERPRETATION: These results show that skeletal muscle NOS activity is impaired during the progression of insulin-deficient diabetes and reduced NOS activity is associated with a decreased abundance of both nNOS and eNOS proteins, which appears to involve post-transcriptional mechanisms [22].
• After 1 week of diabetes, eNOS protein content was decreased only in the plasma membrane whereas nNOS protein abundance was not affected at this time [22].
• Also, denervated and immediately reinnervated muscle fibers showed decreased expression of nNOS [17].
• The ratio of NOS activity to nNOS mRNA was significantly higher in hippocampus and cerebellum of aged brain [23].

Associations of Nos1 with chemical compounds

• In corticosterone rats, Nos2 mRNA decreased in cortex by 68+/-5% and in medulla by 62+/-6%; Nos3 mRNA by 50+/-8% in cortex, and Nos1 by 29+/-7% in medulla (all P<0.001 after Hochberg correction) [21].
• CaV1p1 inhibited NO formation activity and NADPH oxidation of wild-type nNOS in a dose-dependent manner with an IC(50) value of 1.8 microM [16].
• Addition of 1.0 mmol/L EDTA to the reaction decreased NOS activity to <5 pmol. mg(-1). h(-1) in afferent arterioles, glomeruli, and vasa recta (n=5 each), indicating that the NOS enzymatic activity in these segments is primarily a result of constitutive NOS [24].
• Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance [1].
• Recently, we reported nitroarginine-containing dipeptide amides (Huang, H; Martasek, P.; Roman, L. J.; Masters, B. S. S.; Silverman, R. B. J. Med. Chem. 1999, 42, 3147.) and some peptidomimetic analogues (Huang, H; Martasek, P.; Roman, L. J.; Silverman, R.B. J. Med Chem. 2000, 43, 2938.) as potent and selective inhibitors of neuronal NOS (nNOS) [25].

Physical interactions of Nos1

• The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord [26].
• The results indicate that distention of the stomach was due to inhibition of neuronal NOS activation by a direct interaction between cisplatin and the calcium binding sites of the calmodulin molecule [27].

Co-localisations of Nos1

• Results of immunohistochemical studies showed that nNOS colocalized with the neuronal marker MAP-2 at all time points, whereas iNOS was initially localized to vessels, and then localized to activated microglia by 24 hours [28].

Regulatory relationships of Nos1

• Caveolin is known to down-regulate both neuronal (nNOS) and endothelial nitric-oxide synthase (eNOS) [16].
• Cyclical upregulated iNOS and long-term downregulated nNOS are the bases for relapse and quiescent phases in a rat model of IBD [4].
• Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI [11].
• This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure [29].
• The immunohistochemical analysis revealed that the restored renal nNOS expression induced by chronic adrenomedullin infusion may reflect the restoration of nNOS expression in the macula densa and inner medullary collecting duct [30].

Other interactions of Nos1

• In the present study, direct interactions of recombinant caveolin-1 with both the oxygenase and reductase domains of nNOS were demonstrated using in vitro binding assays [16].
• Immunocytochemical studies exhibited distribution of nNOS and iNOS in cytoplasm and nucleus, and L-[3H] citrulline formation and DAF fluorescence confirmed NOS activity in both fractions [31].
• Thus AVP specifically increases nNOS expression levels in the renal outer medulla and papilla [32].
• Western blotting further revealed a dramatic decrease in eNOS protein expression in aged CA2/3 with no age-associated changes in nNOS, arginase I and II protein expression in any region examined [33].
• Therefore, we mapped local mRNA and peptide/protein presence of both Ucn and the NO producing neuronal NO synthase (nNOS) [34].

Analytical, diagnostic and therapeutic context of Nos1

• Neuronal NOS mRNA was detected by RT-PCR in whole bone, but we were unable to detect nNOS protein in bone cells in vivo or in studies of cultured bone-derived cells in vitro [35].
• Oral administration of the specific V(2)-receptor antagonist SR-121463B decreased nNOS expression in the outer medulla and papilla but did not alter eNOS expression levels [32].
• In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR [36].
• Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity) [36].
• Immunoprecipitation studies indicated that hyperoxia doubles the amount of nNOS associated with the molecular chaperone, heat shock protein 90 (Hsp90) [37].

References