Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.19 (NOS)
 7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article assesses the circulating levels of L-arginine, the renal response to L-arginine infusion, and the renal expression of inducible and constitutive nitric oxide synthase (NOS II and NOS III, respectively) in cirrhotic rats with ascites. Systemic and renal hemodynamics and renal function were measured in basal conditions and following two doses of L-arginine (5 and 10 mg x kg(-1) x min for 40 minutes). Renal NOS II and III messenger RNA (mRNA) expression was evaluated in basal conditions by polymerase chain reaction and Northern blot, respectively. Renal NOS II and III protein expression was assessed by Western blot and immunohistochemistry. Plasma concentration of L-arginine was significantly lower in cirrhotic rats than in control rats (48+/-11 vs. 86+/-9 micromol/L, P < .025). In both groups L-arginine infusion had no effect on systemic hemodynamics, but markedly increased renal perfusion. This effect was significantly more intense in cirrhotic rats. A very weak signal of similar intensity was found for NOS II mRNA in both groups of animals. However, no NOS II protein expression was detected. In contrast, higher NOS III mRNA abundance and protein expression, which was mainly located in the endothelial lining of the renal arterioles, were found in the kidney of cirrhotic animals. These results indicated increased renal expression of NOS III mRNA and protein, deficient circulating levels of L-arginine, and increased renal hemodynamic response to this amino acid in cirrhotic rats with ascites. Our results suggest that L-arginine supplementation at doses not affecting arterial pressure could have beneficial effects on renal perfusion in cirrhosis.
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PMID:Increased renal expression of nitric oxide synthase type III in cirrhotic rats with ascites. 958 70

Intracellularly generated reactive species of both oxygen (ROS) and nitrogen (RNS) have been implicated in signaling responses in airway epithelial cells, but these radicals have not been measured directly in such cells. In this study, intracellular production of both ROS and RNS were measured in the same cell lysates of guinea pig tracheal epithelial (GPTE) cells maintained in primary culture. ROS and RNS were quantified under basal (constitutive) conditions and in response to different stimuli: LPS and TNFalpha [activators of inducible nitric oxide synthase (iNOS)]; several activators of calcium-dependent cNOS (ATP, bradykinin, ionophore A23187, and thapsigargin); and exogenous oxidant stress generated by addition of xanthine oxidase to purine (p + XO). Studies with LPS and TNFalpha also were performed using the murine macrophage cell line, RAW 264.7, as a positive control. Intracellular oxidant production was detected from oxidation of dihydrorhodamine to rhodamine. NOx was quantified by either chemiluminescent or fluorescent detection. NOS activity was measured as citrulline production from arginine. Basal production of oxidants by GPTE cells (0.08 + 0.00 nmol rhodamine) was less than 10% that of RAW.267 cells (0.91 + 0.03 nmol rhodamine). TNFalpha and LPS significantly increased intracellular oxidant production in GPTE cells, as did p + XO, but none of the cNOS activators affected production of oxidants in these cells. Concentrations of NO2 after 4 h in unstimulated RAW 264.7 and GPTE cells were similar and comprised 63% of total NOx in GPTE and 62% in RAW cells. TNFalpha and LPS both increased NO2 in GPTE cells, but none of the Ca++-mobilizing agents nor p + XO significantly affected intracellular RNS. The results suggest both ROS and RNS can be measured in the same lysates from airway epithelial cells, and that both ROS and RNS are produced in these cells in response to different stimuli.
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PMID:Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro. 958 18

Mechanical forces generated at the endothelium by fluid shear stress and pulsatile stretch are important in ensuring the continuous release of vasoactive endothelial autacoids. Although the mechanism by which endothelial cells are able to detect and convert these physical stimuli into chemical signals is unclear, this process involves the activation of integrins, G proteins and cascades of protein kinases. The constitutive endothelial nitric oxide synthase (NOS III), classified as a Ca2+/calmodulin-dependent isoform, can be activated by shear stress and isometric contraction in the absence of a maintained increase in [Ca2+]i via a mechanism involving its redistribution within the cytoskeleton/caveolae and the activation of one or more regulatory NOS-associated proteins. Thus it would appear that the intracellular cascades activated by Ca2+-elevating receptor-dependent agonists, such as bradykinin, and hemodynamic stimuli are distinct. Rhythmic vessel distension is also able to elicit the synthesis of superoxide anions and the endothelium-derived hyperpolarizing factor which play a role in modulating arterial compliance in certain vascular beds.
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PMID:Pulsatile stretch and shear stress: physical stimuli determining the production of endothelium-derived relaxing factors. 958 70

Considering the structural similarity between gabexate mesylate (FOY), a drug for serine proteinase-mediated diseases, and L-arginine, the effect of gabexate mesylate on the nitric oxide (NO) pathway has been investigated. Gabexate mesylate inhibits competitively constitutive and inducible NO synthase (cNOS and iNOS, respectively), with Ki values of 1.0 x 10(-4) M and 5.0 x 10(-3) M, respectively, at pH 7.4 and 37.0 degrees C. However, gabexate mesylate is not an NO precursor. Moreover, like other NOS inhibitors, gabexate mesylate increases iNOS mRNA expression in rat C6 glioma cells, as induced by E. coli lipopolysaccharide plus interferon-gamma. Finally, gabexate mesylate inhibits dose-dependently nitrite production (i.e. NO release) in rat C6 glioma cells, as induced by E. coli lipopolysaccharide plus interferon-gamma. Thus, this drug should be administered under careful control, since enzyme inhibition may occur also in vivo.
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PMID:Effect of gabexate mesylate (FOY), a drug for serine proteinase-mediated diseases, on the nitric oxide pathway. 961 Mar 82

The changes in the activities of constitutive nitric oxide (NO) synthase (cNOS) and inducible NOS (iNOS) were investigated in arterial tissues of CCl4-induced cirrhotic adult SD rats. The aortic tissue homogenate were prepared in normal and cirrhotic rats. NOS activity was measured by conversion of 3H-arginine to 3 H-citrulline. The activities of cNOS and iNOS were calculated in terms of presence or absence of Ca2+. The results showed that activities of total NOS, cNOS and iNOS in arterial tissues were all increased significantly in cirrhotic rats as compared with those in normal controls. There was a significant positive correlation between the activities of total NOS and cGMP content in cirrhotic arterial tissues.
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PMID:Nitric oxide synthase activity in arterial tissues of cirrhotic rats. 963 80

We have previously reported that Cu2+ endothelium-dependently dilated rat pulmonary arterial rings in a few minutes by increasing NO production via constitutive endothelial nitric oxide synthase (eNOS) activation in rat pulmonary arterial endothelial cells (Eur. J. Pharmacol., 1997). In the present study, using cultured human pulmonary arterial endothelial cells (HPAEC), we assessed the effects of divalent cations (Cu2+, Mn2+, Zn2+, and Fe2+) on NOS activity in crude cell extracts and intact cells. NO synthase activity was measured by monitoring the conversion of L-[14C] arginine to L-[14C] citrulline. The NOS enzyme in crude HPAEC extract showed similar characteristics to previously reported eNOS from other sources. All the divalent cations tested suppressed the NOS activity in crude cell extract by about 50% at 1 x 10(-4) M, but only Cu2+ from 10(-6) M increased eNOS activation dose dependently with a significant elevation in whole-cell assay. Extracellular Ca2+ was prerequisite to the eNOS activation by Cu2+ in intact cells. Furthermore, we measured NO production determined as NOx (NO, .NO2-, and .NO3-) from HPAEC using NO chemiluminescence analyzer. HPAEC monolayers were treated with either buffer alone, Cu2+ (10(-4) M) or thapsigargin (10(-6) M). The amount of .NOx increased from 10.93 (pmoml/ml/10(6) cells) to 41.27 (pmol/ml/10(6) cells) by thapsigargin (10(-6) M) and to 45.24 (pmol/ml/10(6) cells) by Cu2+ (10(-4) M). The increase in NOx by Cu2+ was inhibited by L-NMMA. These results indicated that Cu2+, but not Mn2+, Zn2+, and Fe2+, causes the activation of eNOS, while Cu2+, Mn2+, Zn2+, and Fe2+ directly suppressed eNOS activity extracted from HPAEC. Further, our study showed that extracellular Ca2+ was essential for eNOS activation by Cu2+.
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PMID:The activation of eNOS by copper ion (Cu2+) in human pulmonary arterial endothelial cells (HPAEC). 968 Jan 77

Monocyte-macrophage series have an important role in host surveillance against cancer. The cytotoxic/cytostatic activity of macrophages is, to a great extent, attributed to the up-regulation of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Here, in 28 patients with primary lung cancer and 20 control subjects, we measured the concentration of exhaled NO and nitrite in epithelial lining fluid (ELF) using a chemiluminescence NO analyser, and studied NOS expression in alveolar macrophages (AM) and lung tissues by flow cytometry; immunohistochemical analysis was also undertaken. The mean fluorescence intensity (FI) of iNOS expression in AM was significantly increased in patients with lung cancer (tumour side 263.5 +/- 15.2 FI, normal side 232.4 +/- 18.6 FI; n = 28) compared with that in control subjects (27.3 +/- 3.2 FI; n = 20, P< 0.001). The level of exhaled NO from cancer patients (16.9 +/- 0.9 p.p.b.; n = 28) was significantly higher than that in the control group (6.0 +/- 0.5 p.p.b.; n = 20, P < 0.001). The level of nitrite was also significantly higher in ELF from cancer patients (tumour side 271.1 +/- 28.9 nM and normal side 257.4 +/- 19.6 nM vs control subjects 32.9 +/- 4.1 nM; P< 0.001). The intensity of iNOS expression in AM was correlated with the level of exhaled NO (rs = 0.73, n = 76, P< 0.001) and the nitrite released in ELF (rs = 0.56, n = 76, P< 0.001). The nitrite generation of cultured AM from patients with lung cancer was significantly enhanced compared with that of control subjects after culture for 24 h (tumour side 5.75 +/- 0.69 and normal side 5.68 +/- 0.58 microM per 106 cells vs control group 38.3 +/- 3.6 nM per 106 cells; P< 0.001). The distribution of iNOS was identified in AM, tumour-associated macrophages, endothelium, chondrocytes, airway epithelium of both lungs and malignant cells (adenocarcinoma and alveolar cell carcinoma) of cancer patients. cNOS was labelled in alveolar macrophages, endothelial cells and nerve elements from lung tissue. Our results indicate that, in patients with primary lung cancer, the production of NO from alveolar macrophages was increased as a result of the up-regulation of iNOS activity. The increased NO production was not specific to the tumour side and might be attributed to the tumour-associated non-specific immunological and inflammatory processes of the host.
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PMID:Increased level of exhaled nitric oxide and up-regulation of inducible nitric oxide synthase in patients with primary lung cancer. 971 40

After removing nonspecific immunoreactivities from crude extract by immunoaffinity chromatography, an immunoreactive-band at 60 kDa of constitutive nitric oxide synthase (cNOS) from Saccharomyces cerevisiae was detected by Western blot using mouse monoclonal anti-neuronal NOS (cNOS). The activity of yeast cNOS, which was prepared by either histone-agarose chromatography or anti-neuronal NOS immunoprecipitation, was monitored by the formation of citrulline. Yeast cNOS was activated in the presence of calmodulin and arginine, whereas it was inhibited by L-NAME, a mammalian NOS inhibitor. Moreover, actinomycin-D decreased the extracellular and the intracellular levels of nitrate and nitrite which had been converted from NO. The results suggest that cNOS occurs in unicellular eukaryotes and the enzyme activity can be regulated.
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PMID:Constitutive nitric oxide synthase in Saccharomyces cerevisiae. 976 6

A decrease in constitutive nitric oxide synthase (cNOS) activity occurred with decreases in hexosamine (an index of mucus synthesis) and adherent mucus (an index of mucus secretion) concentrations in the gastric mucosa of rats with water immersion restraint (WIR) stress. The decreases in gastric mucosal hexosamine and adherent mucus concentrations were enhanced with a further decrease in gastric mucosal cNOS activity by pretreatment with NG-monomethyl L-arginine, a non-selective NOS inhibitor, but were prevented with maintenance of the gastric mucosal cNOS activity by pretreatment with aminoguanidine, a selective inducible NO synthase inhibitor. In all WIR-stressed rats used in this study, gastric mucosal cNOS activity was well correlated with either gastric mucosal hexosamine or adherent mucus concentration (r=0.717 or 0.739, respectively). These results indicate that in the gastric mucosa of WIR-stressed rats, a decrease in cNOS activity is closely related to a decrease in mucus level due to impairment of its synthesis and secretion. (c) 1998 The Italian Pharmacological Society.
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PMID:Relationship between constitutive nitric oxide synthase activity and mucus level in the gastric mucosa of rats with stress. 980 20

This study was designed to investigate changes in mucosal NOS activity after burns and its relation to barrier failure. In Experiment 1, female specific pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dextran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Griess' reagent, and the cellular localization of iNOS was examined using immunostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS activity, intestinal permeability, and barrier function were evaluated. The activity of iNOS increased 24 h after the injury and up to a maximum of twofold on postburn Day 2, and decreased thereafter. The increase in iNOS activity in gut mucosa correlated well with the increase in intestinal permeability, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. In conclusion, thermal injury induces intestinal mucosal iNOS, which is principally in the enterocytes. The increased intestinal iNOS activity was closely related to barrier failure. SMT inhibited intestinal mucosal iNOS activity and prevented barrier failure as demonstrated by a decrease in BT occurrence and intestinal permeability.
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PMID:Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure. 1003 Jul 96


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