Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the involvement of nitric oxide in trinitrobenzene-sulfonic acid (TNB) colitis. Every 24 h after TNB, rats were orally dosed with NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), NG-nitro-D-arginine methyl ester (D-NAME), or water, and food intake, body weight, and plasma nitrite levels were measured. On day 6, colonic nitric oxide synthase and myeloperoxidase (MPO) activity, histology, intestinal muscle growth, NADPH-diaphorase, and myenteric nerve function were assessed. Food intake and body weight were reduced during the first 72 h of colitis. On day 6 post-TNB, a fourfold increase in mucosal nitric oxide synthase, a 30-fold increase in MPO, and a fivefold elevation in plasma nitrite were measured. Smooth muscle hyperplasia and hypertrophy in both colonic muscle layers, numerous diaphorase-positive macrophages in the myenteric plexus, and a suppression of myenteric nerve function were also observed. Unlike D-NAME, oral L-NAME reduced MPO and intestinal muscle hyperplasia by > 90%. Likewise, plasma nitrite and colonic nitric oxide synthase were reduced by > 70%. L-NAME completely prevented macrophage infiltration into the muscle. Conversely, it had no effect on anorexia or intestinal smooth muscle hypertrophy, nor did it affect suppressed myenteric nerve neurotransmitter release. These results demonstrate the selective transmural protective effects of L-NAME in the inflamed colon, implicating nitric oxide as a mediator.
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PMID:The selective beneficial effects of nitric oxide inhibition in experimental colitis. 753 57

Osteoclasts have been shown to destroy calcified tissue by complex developmental steps involving cell recruitment, cell attachment and deployment of multiple enzymes. They also appear to regulate resorption by several mechanisms. In particular, earlier investigations have indicated that oxygen radical metabolites may be produce by osteoclasts. These labile reactants could accelerate destruction of calcified tissue. In addition, recent studies have suggested that nitric oxide may have an inhibitory role in bone resorption. Previous studies of these radical substituents have predicted that interactions of nitric oxide and oxygen radicals could explain the conflicting roles of these radicals in the control of bone resorption. In view of the requirement of both of the enzymes, NADPH-oxidase and NO synthase (NOS), for NADPH(beta-nicotinamide adenine dinucleotide phosphate), one level of interaction could be related to competition for this necessary cofactor. To test this hypothesis, we have investigated the ability of the osteoclast to generate nitric oxide and oxygen radicals after stimulation by NADPH. Consistent with earlier diaphorase histochemistry, we have shown that resorbing osteoclasts produce NO. Addition of NADPH (10 microM) resulted in a transient burst of NO production (measured by porphyrin coated microsensor) with an amplitude of 152 +/- 43 nM and a duration of 4 seconds. Repetitive stimulation resulted in a decremental response with a partial recovery after 30 minutes. Addition of L-NAME (N omega-nitro-L-arginine methyl ester, 100 microM) to the cells resulted in at least 50% inhibition of the amplitude of NO peak and produced an extended peak duration. To compare the effect of the added NADPH on superoxide production by osteoclast NADPH-oxidase, osteoclast oxygen radicals were detected by EPR(electron paramagnetic resonance) spectrometer with the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The production of a spin adduct with a quadruplet signal was inhibited by SOD (superoxide dismutase). We were not able to demonstrate an increase in superoxide production after addition of L-NAME, another possible interaction of NOS and NADPH-oxidase. These results demonstrate that although osteoclasts produce both NO and superoxide, NOS competition for NADPH is not a major site of interaction with NADPH-oxidase under these conditions. Additionally, these initial findings set the stage for the further investigation of interactions of osteoclast radicals in modulating bone resorption.
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PMID:Osteoclast radical interactions: NADPH causes pulsatile release of NO and stimulates superoxide production. 758 66

In the present experiments we planned to ascertain whether an abnormal production of nitric oxide (NO) by human CHP100 neuroblastoma cells in culture following stimulation of N-methyl-D-aspartate (NMDA) receptors, produced lethal effects in co-cultured human BMEL melanoma cells. Human BMEL melanoma cells in culture were found to be positive to the nicotinamide adenine dinucleotide phosphate diaphorase (NADPH diaphorase) histochemical reaction and produced NO as revealed by measurements of nitrite under basal culture conditions. Exposure for 50 min to aspartate (1-2 mM) or to NMDA (0.5-1.5 mM) did not evoke significant melanoma cell death. The dose of 1.0 mM NMDA applied for 1 min to BMEL cell cultures did not increase significantly nitrite concentrations in comparison to controls. Incubation for 50 min of human CHP100 neuroblastoma cells with NMDA (0.5-1.5 mM) elicited dose-dependent death of BMEL melanoma cells co-cultured in trans-wells. Under these experimental conditions, nitrite levels in cell culture-inserts containing melanoma cells increased by 120% 1 min after application of the excitotoxin (1 mM) to CHP100 neuroblastoma cultures. The lethal effects produced in BMEL cell culture-inserts by application of NMDA (1.0 mM) to CHP100 cultures were prevented by pretreatment of neuroblastoma cultures with MK801 (200 nM). Similar protection was also afforded by N omega-nitro-L-arginine methyl ester (L-NAME; 0.2 mM) and N omega-monomethyl-L-arginine (L-NMMA; 0.2 mM), two inhibitors of nitric oxide synthase, and by haemoglobin (10 microM), a nitric oxide trapping agent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-methyl-D-aspartate-induced excessive formation of nitric oxide in CHP100 neuroblastoma cells produces death of BMEL melanoma cells in co-culture. 783 19

In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received 125I-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D-NAME, 9 mumol) produced no exudative response. Coadministration of L-arginine (27 mumol) abolished the L-NAME-induced exudation. The extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.
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PMID:Mucosal nitric oxide may tonically suppress airways plasma exudation. 802 53

The present study aimed to determine whether nitric oxide synthase (NOS)/nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity would be induced in facial motoneurons after facial nerve avulsion and if so, whether such activity was related to neuronal death commonly observed after such injury. The left facial nerve in each of 28 Wistar albino rats was avulsed from the facial canal. Ten of them received either daily injections of N omega-nitro-L-arginine methyl ether (L-NAME) or the vehicle. After survival times ranging from 2-50 days, serial brainstem sections were processed for NOS immunocytochemistry and NADPH-d histochemistry respectively. The number of surviving, NOS and NADPH-d positive and NOS negative neurons were compared statistically. Two days after facial nerve avulsion, increased NADPH-d activity was noticed in the facial motoneurons and in the endothelial lining of many dilated blood vessels in the facial motor nucleus (FMN). NOS-positive neurons were not detectable until five days after operation. Both the number and staining intensity of NADPH-d and NOS-positive neurons increased steadily with increasing survival time while the number of surviving neurons decreased after nerve avulsion. Daily administration of L-NAME protected 17% the neurons from death in the affected FMN when examined at 30 days after nerve avulsion, suggesting a neurodestructive property of NO. It was also noticed that some of the surviving neurons were first NOS positive but became NOS negative later.
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PMID:The role of nitric oxide in facial motoneuronal death. 858 76

Nitric oxide synthase (NOS) isoenzymes generate nitric oxide (NO), a sensitive multifunctional intercellular signal molecule. High NO levels are produced by an inducible NOS (iNOS) in activated macrophages in response to proinflammatory agents, many of which also regulate local bone metabolism. NO is a potent inhibitor of osteoclast bone resorption, whereas inhibitors of NOS promote bone resorption both in vitro and in vivo. The possibility that osteoclasts, like macrophages, express a regulated iNOS and produce NO as a potential autocrine signal following inflammatory stimulation was investigated in well-characterized avian marrow-derived osteoclast-like cells. NO production (reflected by medium nitrite levels) was markedly elevated in these cells by the proinflammatory agents lipopolysaccharide (LPS) and the synergistic action of IL-1 alpha, TNF alpha, and IFN gama. inhibitors of NOS activity (aminoguanidine, L-NAME) or iNOS induction (dexamethasone, TGF beta) reduced LPS-stimulated nitrite production. LPS also increased the NOS-associated diaphorase activity of these cells and their reactivity with anti-iNOS antibodies. RT-PCR cloning, using avian osteoclast-like cell RNA and human iNOS primers, yielded a novel 900 bp cDNA with high sequence homology (76%) to human, rat, and mouse iNOS genes. In probing osteoclast-like cell RNA with the PCR-derived iNOS cDNA, a 4.8 kb mRNA species was detected whose levels were greatly increased by LPS. Induction of iNOS mRNA by LPS, or by proinflammatory cytokines, occurred prior to the rise of medium nitrite in time course studies and was diminished by dexamethasone. Moreover, osteoclast-like cells demonstrated an upregulation of NO production and iNOS mRNA by IL-8 and IL-10, regulatory mechanism's not previously described. It is concluded that osteoclast-like cells express a novel iNOS that is upregulated by inflammatory mediators, leading to NO production. Therefore, NO may serve as both a paracrine and autocrine signal for modulating osteoclast bone resorption.
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PMID:Proinflammatory agents, IL-8 and IL-10, upregulate inducible nitric oxide synthase expression and nitric oxide production in avian osteoclast-like cells. 870 87

The inner sublayer (P-layer) of the circular muscle coat in the canine proximal colon has been known to produce spontaneous mechanical contractions associated with characteristic electrical activities called slow waves. We recorded the mechanical activities of tissue preparations from this P-layer. Normal Krebs solution (K+; 6 mM) was used as the perfusate. Elevation of extracellular K+ concentrations in the range of 12 mM and 36 mM induced intensified phasic contractions. Administration of an NO-synthase inhibitor, N omega-nitro-arginine methyl ester (L-NAME, 50 microM), enhanced both the spontaneous mechanical rhythms and high extracellular K(+)-induced contractions. Administration of the substrate for NO synthases, L-arginine (400 microM) remarkably suppressed the effects of L-NAME on the amplitude of the spontaneous rhythms and on responses to extracellular high K+. Histological structures of nerves in the P-layer were investigated by an NADPH (nicotinamide adenine dinucleotide phosphate)-diaphorase technique and by the immunohistochemistry of NO-synthases, since NO-producing (nitrinergic) nerves usually, if not always, show a histochemical NADPH-diaphorase positive reaction in formaldehyde-fixed specimens, and since features of ganglia and nerve strands in the outer subdivision of the submucosal plexus (plexus submucosus externus; or so-called Henle's plexus) together with the delicate network of nerve terminal varicosities within the P-layer were clearly visualized by this method. The topographical arrangement of nitrinergic nerves supported the view that they produce nitric oxide (NO), being one of the major chemical mediators of the neural control of the spontaneous rhythms in the P-layer.
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PMID:Nitrinergic nerves controlling pacemaker activities of the inner sublayer (P-layer) in the canine proximal colon circular muscles. 872 61

The principal goal of the present study was to test the hypothesis that cytokines modulate glucose transport in skeletal muscle by increasing nitric oxide production. Cultured L6 skeletal muscle cells were incubated in the presence of tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone or in combination for 24 h. Neither cytokines nor LPS alone induced NO production, as measured by nitrite concentrations in the medium. However, when used in combination, the two cytokines significantly stimulated NO production, and this effect was synergistically enhanced by the presence of LPS. Reverse transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in iNOS expression was confirmed at the protein level by Western-blot analysis and NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose transport, but significantly less in cells chronically exposed to cytokines/LPS. The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in cytokine/LPS-treated cells, and this prevented the increase in basal glucose transport and restored muscle cell responsiveness to insulin. Cytokines/LPS exposure significantly increased GLUT1 transporter protein levels but decreased GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1 protein content but failed to restore GLUT4 transporter levels. These results demonstrate that cytokines and LPS affect glucose transport and insulin action by inducing iNOS expression and NO production in skeletal muscle cells. The data further indicate that cytokines and LPS increase the expression of the GLUT1 transporter protein by an NO-dependent mechanism.
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PMID:Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. 923 Jan 32

The present study was undertaken to investigate the role of nitric oxide (NO) in erectile physiology by correlating its action with the existence and activity of nitric oxide synthase (NOS), which produces NO. We applied Western blot analysis in both human and rat penile tissue. In the rat, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and spectrophotometric assay were also performed, in addition to in vivo electroerection study with pharmacological manipulation. Western blot analysis identified a protein of 155 KDa identical to the neural form of NOS in the human and rat penis. The NOS blot densities in the two species were similar, and both were lower than that in the rat cerebellum. Histochemical staining localized NOS to neurons innervating the corpora cavernosa, including the pelvic plexus, the cavernosal nerves and their terminal fibers within the corporeal erectile tissue, and dorsal penile nerves. NOS activity was also found in the cerebellum, urethra, penis, and urinary bladder, in decreasing order of intensity. Intracavernous injections of NOS inhibitor (L-NOARG or L-NAME in concentrations from 10(-6) M to 10(-3) M suppressed electrostimulation-induced erection in a concentration-dependent manner. Subsequent intracavernous injection of L-Arginine (10(-2) M) partially restored the erection. The neural form of constitutive NOS in the corpora cavernosa synthesizes NO, which mediates penile erection. Determination of cavernosal NOS expression or activity may permit characterization of certain pathological conditions that cause impotence.
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PMID:Role of nitric oxide in penile erection. 940 89

The significance of nitric oxide (NO) formation in seminal secretion was studied in guinea-pig seminal vesicles. The nitric oxide synthase (NOS) activity was estimated and reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was performed. Furthermore, cyclic guanosine 3,5-monophosphate (cGMP) concentration as well as fructose secretion from isolated vesicles was estimated. High Ca2+-dependent NOS activity as well as prominent glandular NADPH-diaphorase staining was found in the secretory epithelium. The NOS inhibitors N(G)-nitro L-arginine methyl ester (L-NAME) and N(G)-nitro L-arginine (L-NNA) inhibited carbachol-induced fructose secretion but the D-isomer to L-NAME had no effect. When L-arginine was administered together with L-NAME, no inhibitory effect on the carbachol-induced fructose secretion could be seen. Nerve-induced fructose secretion was also inhibited by L-NAME. The NO donor glyceryl trinitrate (GTN) increased the fructose secretion. Carbachol or GTN did not increase cGMP levels, nor was fructose secretion inhibited by a guanylate cyclase inhibitor (ODQ). Our results suggests that glandular NO production is a prerequisite for muscarinic fructose secretion in the seminal vesicle via a cGMP-independent pathway.
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PMID:Is glandular formation of nitric oxide a prerequisite for muscarinic secretion of fructose in the guinea-pig seminal vesicle? 944 54


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