Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: CAS:74-79-3 (arginine)
96,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We recently demonstrated that NG-hydroxy-L-arginine (L-HOArg) is a substrate for the constitutive nitric oxide (NO) synthase present in bovine aortic endothelial cells cultured on microcarrier beads (EC). Furthermore, L-HOArg reacts chemically with NO released from these cells to form a potent and more stable vasodilator. This is most likely through a reaction with the hydroxyguanidino group. 2. Here, we studied the interaction of a simpler molecule, hydroxyguanidine (HOG) with NO. 3. HOG (10 microM), like L-HOArg (10 microM) or NG-hydroxy-D-arginine (D-HOArg, 10 microM), potentiated and stabilized the relaxant activity of authentic NO. 4. When NO was bubbled through the solution of HOG, a new compound was formed. It had similar physicochemical properties to those of the previously described L-HOArg/NO adduct. It was also a potent vasodilator and its action was inhibited by oxyhaemoglobin (10 microM), indicating formation of a NO-containing substance. 5. Moreover, HOG (10 microM) was not a substrate for the constitutive NO synthase present in the microsomal fraction of EC and did not affect the flow-induced or bradykinin-stimulated generation of prostacyclin, as measured by 6-keto-PGF1 alpha. 6. We also studied the effect of HOG on the endothelium-derived relaxing factor (EDRF) released from the column of EC. HOG (10 microM) potentiated and stabilized the relaxations of rabbit aortic strips induced by EDRF released by bradykinin (5-20 pmol) or ADP (5-10 nmol). These relaxations were inhibited by NG-nitro-L-arginine methyl ester (L-NAME, 10 microM) and L-arginine (L-Arg, 1 mM) reversed the inhibitory effects of L-NAME. 7. HOG (10 iM) augmented the basal (flow-induced) EC-dependent relaxations which were also inhibited by L-NAME (10 1M) and the effects of L-NOArg were reversed by L-Arg (1 mM).8. Thus, the hydroxyguanidino moiety of L-HOArg is involved in the reaction with NO. Moreover, the comparable reaction of the hydroxyguanidino compounds with NO on the one hand and with flowinduced and agonist-triggered EDRF on the other, strongly supports their common identity.
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PMID:Potentiation of the vasorelaxant activity of nitric oxide by hydroxyguanidine: implications for the nature of endothelium-derived relaxing factor. 128 16

1. The synthesis of nitrite and citrulline from L-arginine by immune-stimulated rat alveolar macrophages and the modulation of this synthesis were studied. 2,4-Diamino-6-hydroxypyrimidine (DAHP), 6R-5,6,7,8-tetrahydro-L-biopterin (BH4) and L-sepiapterin were potent inhibitors of the recombinant interferon-gamma induced production of nitrogen oxides in intact cultured cells with I50 values for BH4 and L-sepiapterin of approximately 10 microM. They were equally effective in inhibiting the induced production of citrulline. This inhibitory effect was concentration-dependent for all three modulators investigated. 2. The inhibitory effects were not dependent on incubation times of either 24 or 48 h, on the immune-stimulus used (lipopolysaccharide, interferon-gamma), or whether these stimuli were added during or after the induction period. 3. Pterin-6-carboxylic acid (PCA), which cannot be converted into BH4, and methotrexate (MTX), which inhibits dihydrofolatereductase but not de novo biosynthesis of BH4, did not change the production of nitrite. 4. The data indicate that DAHP, an inhibitor of the de novo biosynthesis of the co-factor BH4, blocks the nitric oxide synthase activity in intact cells. Since the pterins BH4 and L-sepiapterin blocked the L-arginine dependent production of nitrite and citrulline, the activity of nitric oxide synthase in phagocytic cells may be regulated by metabolic endproducts of the de novo biosynthesis of BH4.
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PMID:Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages. 128 17

L-Arginine (> or = 30 mg kg-1, i.v.), but not D-arginine (300 mg kg-1) administered 5 min after unilateral common carotid/middle cerebral artery occlusion increased regional cerebral blood flow (rCBF) within the dorsolateral ischaemic cortex in spontaneously hypertensive rats. L-Arginine (300 mg kg-1) increased rCBF from 22 +/- 2.7 to 33 +/- 4% of baseline as measured by laser-Doppler flowmetry. This increase may explain the ability of L-arginine to reduce infarct size following focal cerebral ischaemia, as reported previously. The mechanism appears to be mediated by nitric oxide since topical L-NAME (1 microM), a nitric oxide synthase inhibitor, decreased pial arteriole calibre from 115 +/- 2.2 to 106 +/- 0.9% of baseline following L-arginine infusion (300 mg kg-1).
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PMID:L-arginine dilates rat pial arterioles by nitric oxide-dependent mechanisms and increases blood flow during focal cerebral ischaemia. 128 21

The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids.
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PMID:Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. 128 71

1. In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide synthase was determined biochemically and immunochemically. 2. In the rat brain, the highest nitric oxide synthase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG-nitro-L-arginine or NG-methyl-L-arginine. 3. Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity. 4. These results indicate that the ferret brain contains a nitric oxide synthase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain.
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PMID:Nitric oxide synthase in ferret brain: localization and characterization. 128 76

We have recently shown that transforming growth factor-beta (TGF beta) acts in an autocrine manner to maintain the beating rate of neonatal rat cardiac myocytes cultured in serum-free medium on cardiac fibroblast matrix. Interleukin-1 beta (IL-1 beta) suppresses the myocyte-beating rate, and TGF beta antagonizes this effect. We now show that TGF beta and IL-1 beta also have antagonistic effects on the secretion of nitric oxide (NO) by these myocytes, and that NO secretion, the activity of NO synthase (NOS), and expression of the inducible form of NOS correlate inversely with the effects of these two agents on the beating rate. Western blot analysis shows that treatment of myocytes with TGF beta antagonizes the induction of NOS after treatment with IL-1 beta. Release of NO, induced by IL-1 beta, is dependent upon the availability of the substrate, L-arginine, and is suppressed by a competitive inhibitor, NG-monomethyl-L-arginine. L-Arginine (> 0.25 mM) also suppresses, and NG-monomethyl-L-arginine (> 0.5 mM) enhances the myocyte-beating rate. Treatment with IL-1 beta, but not TGF beta, increases cellular cGMP, presumably by activation of guanylate cyclase by NO. Methylene blue, an inhibitor of guanylate cyclase, reverses the suppression of beating caused by IL-1 beta. Bacterial lipopolysaccharide, present in the serum-free medium, is a coinducer of NO secretion. The suppressive effects of NO on the beating rate can be overcome by altering either the set of cytokines employed to induce NO or the matrix on which the myocytes are cultured, demonstrating that additional parameters are also involved in regulation of the beating rate.
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PMID:Role of nitric oxide in antagonistic effects of transforming growth factor-beta and interleukin-1 beta on the beating rate of cultured cardiac myocytes. 128 74

The nitric oxide (NO) synthase activity present in murine J774.2 monocyte/macrophages was characterized in terms of its intracellular localization, substrate specificity, and Ca2+ dependency. Traces of constitutive NO synthase activity were found in the microsomal fraction from noninduced J774.2 cells, whereas no NO synthase activity was detected in the cytosol. After 24 h in the presence of bacterial lipopolysaccharide and mouse interferon, NO synthase activity was substantially increased in both fractions with 51-60% of the total activity present in the cytosol. These activities, however, were clearly different, for the microsomal enzyme was Ca2+ dependent, whereas the cytosolic NO synthase was not. Moreover, NG-hydroxy-L-arginine (L-HOArg), L-homo-arginine, and several L-arginine (L-Arg)-containing dipeptides could replace L-Arg as substrates for the Ca(2+)-independent NO synthase, whereas the Ca(2+)-dependent enzyme accepted only L-Arg, L-HOArg, or L-Arg-L-Arg as substrates. Thus, a microsomal Ca(2+)-dependent NO synthase is induced in J774.2 monocyte/macrophages with a substrate specificity different from the inducible Ca(2+)-independent NO synthase as well as the constitutive NO synthase in, for example, endothelial cells. Irrespective of their intracellular localization, therefore, at least three isoforms of NO synthase exist, all of which can accommodate substrates different from L-Arg in size, charge, and hydrophobicity.
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PMID:Characterization of a microsomal calcium-dependent nitric oxide synthase in activated J774.2 monocyte/macrophages. 128 50

Inducible nitric oxide (NO) synthase in vascular smooth muscle cells (SMCs) appears to play a major role for the diminished responsiveness to vasoconstrictors observed in endotoxemia. However, cardiovascular dysfunctions associated with septic shock are also observed in the absence of endotoxin (LPS). Similar hemodynamic changes are produced either by a gram-negative bacteria (Escherichia coli) or by a gram-positive bacteria (Staphylococcus aureus), a microorganism without LPS, suggesting a common pathway leading to cardiovascular abnormalities. In the present study, we describe the induction of NO synthase in vascular SMCs by lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria. In cultured vascular SMCs, a 24-h incubation with LTA produced an increase in intracellular cyclic GMP. This effect was inhibited by methylene blue (MB), an inhibitor of guanylate cyclase. Incubation with a specific inhibitor of L-arginine, i.e., NG-nitro-L-arginine methyl ester (L-NAME), or depletion of L-arginine attenuated the LTA-induced cGMP production. A 5-h incubation of endothelium-free rings of rat aorta in the presence of LTA induced a loss of tonicity to the contractile response of phenylephrine. The contractions were restored by MB and by L-NAME. The effect of L-NAME was reversed by L-arginine. These results show that LTA, like LPS, expresses NO synthase in vascular SMCs.
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PMID:Lipoteichoic acid: a new inducer of nitric oxide synthase. 128 52

Bovine endothelial cells (ECs, P1) and lipopolysaccharide/gamma-interferon-induced mouse macrophages (MMs) were incubated in the presence of SIN-1 and C 3754 (1 microM to 1 mM), sydnonimine metabolites of the antianginal predrugs molsidomine and pirsidomine, respectively up to 48 h. No change of the endogenous nitric oxide output from MMs and A23187- or adenosine triphosphate-stimulated ECs was found by means of the methemoglobin method. Data indicate that downregulation of the nitric oxide (NO) synthase is not obvious within the intact cells under exogenous NO stress supplied by high concentrations of the spontaneous NO donors. Cytosolic MM NO synthase extracts, however, revealed reduction in the enzymic [3H]arginine turnover to [3H]citrulline by SIN-1, but not by C 3786, the pharmacologically active metabolite of pirsidomine.
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PMID:Exogenous nitric oxide stress on endothelial cells and macrophages. 128 53

The aim of the present experiments was to test the possible involvement of nitric oxide (NO) in cytokine-induced enhancement of tumor cell (TC) adhesion to endothelial cells (ECs). Exposure of EA hyb 926 cells to TNF (500 U/ml) plus IFN (100 U/ml) for 24 h significantly enhanced their adhesivity for the 51Cr-labeled GLC1 (small cell lung carcinoma) TCs. Conversely, exposure of TCs to cytokines did not result in an increased adhesion of these cells to ECs. TC-stimulated adhesion to EA hyb 926 was abrogated by the glucocorticoid dexamethasone (Dex, 10(-7) M), the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) and NG-monomethyl-L-arginine (L-NMMA, 10(-5) M) and the protein synthesis inhibitor cycloheximide (Cex, 10(-6) M). Furthermore, GLC1-stimulated adhesion to EA hyb 926 was reversed following removal of L-arginine from the medium or pretreatment with the guanylate cyclase inhibitor methylene blue. TC-stimulated adhesion was also prevented when TCs were pretreated with the monoclonal antibody CD15 directed against the endothelial-leukocyte adhesion molecule (ELAM-1) ligand or following exposure of ECs to anti-ELAM-1 monoclonal antibody. Although suppressing TC-stimulated adhesion, L-NMMA failed to modify significantly cytokine-induced ELAM-1 expression in EA hyb 926. These results (a) provide evidence for the NO-inducible pathway contributing to cytokine-induced enhancement of tumor cell adhesion to the vascular endothelium and (b) demonstrate the involvement of the ELAM-1/CD15 adhesion system in tumor cell-stimulated adhesion to ECs.
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PMID:Involvement of nitric oxide in tumor cell adhesion to cytokine-activated endothelial cells. 128 56


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