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)

The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats.
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PMID:Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat. 129 60

The cell surface cAMP chemotactic receptor of D. discoideum can be phosphorylated in partially purified plasma membrane preparations in a ligand-dependent manner. CAR-kinase, the enzyme responsible for receptor phosphorylation, was shown to be an integral membrane protein. It could utilize either ATP or GTP to phosphorylate the receptor, although ATP was much more efficient. The apparent affinity constant for ATP was approximately 20-25 microM. Maximum CAR-kinase activity was observed between pH 6.5 and pH7, and required the presence of Mg2+. Neither Mn2+ nor Ca2+ could substitute for that divalent cation. The enzyme was found to be sensitive to the ionic strength and temperature of the incubation reaction. Dephosphorylation of the receptor was not observed in the membrane preparations, indicating that the enhanced level of receptor phosphorylation that occurred upon ligand binding was not an indirect reflection of receptor dephosphorylation and subsequent incorporation of radiolabeled phosphate.
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PMID:Properties of CAR-kinase: the enzyme that phosphorylates the cAMP chemotactic receptor of D. discoideum. 208 81

The aim of this study was to examine the influence of vascular endothelium on the relaxation induced by increased extracellular Mg2+ concentrations on isolated and noradrenaline-precontracted aorta from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and normotensive rats. In Mg(2+)-free physiologic salt solution (PSS), addition of Mg2+ (0.1-6.0 nM) caused concentration-dependent relaxation of noradrenaline-precontracted aorta with intact or disrupted endothelium. Mg(2+)-induced relaxation in intact aorta, however, was less in DOCA-salt hypertensive rats than in normotensive rats. When endothelium was disrupted, Mg(2+)-induced relaxation was depressed in aorta from both DOCA-salt hypertensive and normotensive rats. The same observations were made in presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor nitric oxide (EDRF/NO) biosynthesis. Mg(2+)-induced relaxation following contraction with noradrenaline was significantly less in intact aorta treated with L-NAME from DOCA-salt hypertensive rats than in intact aorta from normotensive rats. Indomethacin did not affect Mg(2+)-induced relaxation in intact aorta from normotensive rats whereas indomethacin significantly increased it in DOCA-salt hypertensive rats. It is concluded that (1) Mg(2+)-induced relaxation can be mediated by endothelium-dependent mechanisms implicating EDRF/NO; (2) the influence of EDRF/NO is more pronounced on the impaired Mg(2+)-induced relaxation of aorta from DOCA-salt hypertensive rats; (3) Mg(2+)-induced relaxation seems masked by vasoconstrictor prostaglandin release in DOCA-salt hypertensive rats; (4) these differences between normotensive and hypertensive rats could be related to the impaired endothelial function in aorta from DOCA-salt hypertensive rats.
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PMID:Influence of endothelium on Mg(2+)-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat. 808 52

Magnesium sulfate (MgSO4) has been proposed to be an efficient treatment in persistent pulmonary hypertension of the newborn. We compared the ability of MgSO4 to inhibit the responses to several vasoconstrictors in isolated intrapulmonary and mesenteric arteries from 10-17-d-old piglets. MgSO4 (3-100 mM) produced a slight vasodilator effect in pulmonary arteries precontracted with the thromboxane A2 mimetic U46619 (10(-6) M), noradrenaline (10(-5) M), and KCl (80 mM) (15.1 +/- 3.7%; 20 +/- 3.33%; 10.4 +/- 0.9% at 100 mM MgSO4 respectively). In contrast, in mesenteric arteries MgSO4, produced a marked vasodilation (80.4 +/- 4.0%, 93.1 +/- 3.46%, and 87.5 +/- 1.93% at 100 mM MgSO4, respectively, p < 0.01 versus pulmonary arteries). The vasodilator effect of MgSO4 was endothelium-independent and reversed by increasing the extracellular Ca2+ concentration. After incubation for 1 h of pulmonary arteries with three different MgSO4 concentrations (0, 1.2, and 4.8 mM) there were no differences in the contractile responses to U46619 nor in the vasodilator effects of acetylcholine or sodium nitroprusside. Rapid removal of Mg2+ from bath medium produced a transient vasodilation which was more marked in pulmonary than in mesenteric arteries and was greatly reduced by the removal of endothelium or by the nitric oxide synthase inhibitor L-NAME (10(-4) M). We conclude that MgSO4 is a poor vasodilator of pulmonary arteries in vitro and at physiologic concentrations appears to inhibit nitric oxide release from the pulmonary endothelium. Thus, the possible beneficial clinical effects of MgSO4 in persistent pulmonary hypertension of the newborn do not seem to be related to a direct effect on pulmonary vascular smooth muscle.
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PMID:In vitro effects of magnesium sulfate in isolated intrapulmonary and mesenteric arteries of piglets. 872 78

1. We investigated the role of nitric oxide (NO) in modulating spinal synaptic responses evoked by electrical and noxious sensory stimuli in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord preparation or spinal cord-saphenous nerve-skin preparation of 0- to 2-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or by noxious skin stimulation. 3. In the spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced mono-synaptic reflex followed by a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of NO gas-containing medium (10(-4)- 10(-2) dilution of saturated medium) and NO donors, 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC12, 3-300 microM), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-300 microM) and S-nitroso-L-glutathione (GSNO, 3-300 microM), produced an inhibition of the slow VRP and a depolarization of ventral roots. Another NO donor, 3-morpholinosydononimine (SIN-1, 30-300 microM), also depressed the slow VRP but did not depolarize ventral roots. These agents did not affect the mono-synaptic reflex. 4. In the spinal cord-saphenous nerve-skin preparation, application of capsaicin (0.1-0.2 microM) to skin evoked a slow depolarizing response of the L3 ventral root. This slow VRP was depressed by NOC12 (10-300 microM) and SIN-1 (100-300 microM). When the concentration of NOC12 was increased to 1 mM, spontaneous synaptic activities were augmented and the depressant effect of NOC12 on the slow VRP became less pronounced. 5. A NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide( carboxy- PTIO, 100-300 microM) prevented the depressant effect on the dorsal root-evoked slow VRP and ventral root depolarizing effects of NO donors. Carboxy-PTIO increased spontaneous synaptic activities and markedly potentiated the slow VRP. A NO synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 0.03-1 microM), but not D-NAME (0.03-1 microM), also markedly potentiated the slow VRP and this effect was reversed by L-arginine (300 microM). 6. 8-Bromo-cyclic guanosine 3': 5'-monophosphate (8-Br-cyclic GMP, 100-300 microM) produced both an inhibition of the slow VRP and a depolarization of ventral roots. A cyclic GMP-dependent protein kinase inhibitor, KT5823 (0.3 microM), partly inhibited the depressant effects of NO donors and 8-Br-cyclic GMP on the dorsal root-evoked slow VRP. In contrast, KT5823 did not inhibit the depolarizing effects of NO donors. 7. Perfusion of the spinal cord with medium containing tetrodotoxin (0.3 microM) and/or low Ca2+ (0.1 mM)-high Mg2+ (10 mM) markedly potentiated the depolarizing effect of NO donors. The SNAP-evoked depolarization in the tetrodotoxin-containing low Ca(2+)-high Mg2+ medium was significantly inhibited by excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). 8. The present study suggests that inhibitory and excitatory mechanisms meditated by the NO-cyclic GMP cascade are involved in the primary afferent fibre-evoked nociceptive transmission in the neonatal rat spinal cord. The inhibitory mechanism, but not the excitatory mechanism, appears to be partly mediated by cyclic GMP-dependent protein kinase. It is also suggested that Ca(2+)-independent release of excitatory amino acid neurotransmitters contributes to the depolarizing response to NO of ventral roots.
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PMID:The excitatory and inhibitory modulation of primary afferent fibre-evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide. 884 40

The effects of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, were examined on Mg2+-free-induced epileptiform activity, in guinea-pig piriform cortex slices in vitro. L-NAME (0.1-1 mM) had no effect on neuronal membrane properties or electrically-evoked postsynaptic potentials (PSPs). In contrast, during superfusion of the slices with Mg2+-free solution neurones exhibited spontaneous and stimulus-evoked epileptiform potentials that were suppressed in the presence of L-NAME (100 microM) or the selective NMDA receptor antagonist DL-APV (100 microM). The inhibitory effects induced by L-NAME were reversibly reduced by L-arginine (1 mM), but not D-arginine (1 mM), the latter drug not being a substrate for NO formation. It was concluded that L-NAME can suppress epileptiform activity induced by Mg2+-free exposure primarily through a decrease in presynaptic transmitter release, although additional actions on the NMDA-receptor complex were also considered.
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PMID:Inhibition of nitric oxide synthase prevents magnesium-free-induced epileptiform activity in guinea-pig piriform cortex neurones in vitro. 910 60

1 L-NG-nitro-arginine methyl ester (L-NAME; 100 microM), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 microM acetylcholine (ACh) and 2-10 mM Mg2+ in endothelium-intact (+E) rat aortic rings precontracted with 1 microM phenylephrine (PE). In PE-precontracted endothelium-denuded (-E) rat aorta, 3 microM ACh did not, but Mg2+ caused relaxation which was reversed by L-NAME, but not by D-NAME. 2 The concentration response profiles of L-NAME in reversing the equipotent relaxation induced by 5 mM Mg2+ and 0.2 microM ACh were not significantly different. 3 L-NAME (100 microM) also reversed Mg(2+)-relaxation of -E aorta pre-contracted with 20 mM KCl or 10 microM prostaglandin F2alpha (PGF2alpha). L-NG-monomethyl-arginine (L-NMMA; 100 microM) was also effective in reversing the Mg(2+)-relaxation. 4 Addition of 0.2 mM Ni2+, like Mg2+, caused relaxation of PE-pre-contracted -E aorta, which was subsequently reversed by 100 microM L-NAME. 5 Reversal of the Mg(2+)-relaxation by 100 microM L-NAME in PE-precontracted -E aorta persisted following pre-incubation with 1 microM dexamethasone or 300 microM aminoguanidine (to inhibit the inducible form of NOS, iNOS). 6 Pretreatment of either +E or -E aortic rings with 100 microM L-NAME caused elevation of contractile responses to Ca2+ in the presence of 1 microM PE. 7 Our results suggest that L-NAME exerts a direct action on, as yet, unidentified vascular smooth muscle plasma membrane protein(s), thus affecting its reactivity to divalent cations leading to the reversal of relaxation. Such an effect of L-NAME is unrelated to the inhibition of endothelial NOS or the inducible NOS.
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PMID:L-NAME inhibits Mg(2+)-induced rat aortic relaxation in the absence of endothelium. 1051 Apr 63

Potentiation of the delayed (Glu)-induced neurotoxicity by serum albumin (SA) was studied in experiments with cultured cerebellar granule cells. The delayed neuronal death (DND) was evaluated by counting neurons containing or excluding Trypan Blue 4 h after treatment with Glu. Cytoplasmic Ca2+ ([Ca2+]i) was measured in individual Fura-2-loaded neurons. It was shown that a 15-min application of bovine SA (4 mg/ml) together with Glu (100 microM, 10 microM glycine, Mg2+-free solution) enhanced DND in the culture 1.7 times (43.1+/-3.1%) with respect to the effect induced by Glu alone (24.6+/-0.6%). The bovine SA application did not change the dynamics of [Ca2+]i response during a short-term (1 min) and long-term (15 min) Glu-treatment. DND was prevented by simultaneous application of Glu and inhibitor of NO-synthase N omega-nitro-L-arginine methyl ester (L-NAME), 100 microM) (10.8+/-1.0%) as well as by the application of Glu with SA and L-NAME (9.8+/-1.2%). In order to evaluate the role of nitric oxide (NO) in the SA effect, the cells were incubated for 15 min with the NO-donors sodium nitroprusside (SNP, 10 and 100 microM) and sodium nitrite (NaNO2, 10 and 100 microM) together with SA and in its absence. SA also greatly enhanced the DND induced by SNP and NaNO2. Thus, the DND after simultaneous treatment with SA and SNP was 16.3+/-2.5% (10 microM) or 29.6+/-2.1% (100 microM), and 9.6+/-0.8% (10 microM) and 19.7+/-2.1% after treatment with SNP alone. Exposure to SA together with NaNO2 led to the DND increase up to 26.5+/-1.9% (10 microM) and 37.7+/-3.5% (100 microM) in comparison with 7.4+/-2.0% (10 microM) and 18.9+/-0.8% (100 microM) in experiments with NaNO2 alone. Taking into account the ability of NO and NO2 to oxidize unsaturated fatty acids and the ability of SA to bind them after their hydrolytic removal, we suggested that the SA-induced potentiation of Glu neurotoxicity resulted from exacerbation of the toxic effects of NO and other trace radicals on the neuronal membranes. This hypothesis was supported by the finding that SA also enhanced the neurotoxicity of the lipid prooxidant FeCl2. The simultaneous 15-min application of FeCl2 (10 microM) and SA caused a 51.5+/-4.0% increase in DND, which exceeded 2.4 times the effect produced by FeCl2 alone (21.3+/-2.3%).
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PMID:The mechanism of potentiation of the glutamate-induced neurotoxicity by serum albumin. A possible role of nitric oxide. 1076 89

The production of nitric oxide (NO) during low-Mg2+-induced epileptiform activity in rat hippocampal-entorhinal cortex slices was investigated by real-time monitoring using 1,2-diaminoanthraquinone (DAQ). NO reacts with the aromatic amino groups of DAQ at neutral pH and in the presence of oxygen to form the fluorescence product 1H-anthra-[1,2d]-[1,2,3]triazole-6,11-dione (ATD). The DAQ-induced formation of ATD required NO and was insensitive to radical oxygen species. Removal of Mg2+ ions from the artificial cerebrospinal fluid (ACSF) induced a significant elevation in the ATD fluorescence signal. The application of L-arginine (2 mM), a substrate of nitric oxide synthase (NOS), caused a comparable increase in the ATD fluorescence signal. Furthermore, ATD signal increase induced either by low-Mg2+ ACSF or by L-arginine was sensitive to N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. The application of L-NAME (200 microM) caused a complete blockade of low-Mg2+-induced epileptiform activity. Under this condition, increasing NO concentration by addition of the NO donor S-nitroso-N-acetylpenicillamine (200 microM) reinduced the epileptiform activity. It has been concluded that onset and maintenance of low-Mg2+-induced spontaneous epileptiform activity are modulated by NO concentration. Further NO imaging studies may help to elucidate the role of NO in detail and may bring to light new means for epilepsy therapy.
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PMID:Nitric oxide modulates low-Mg2+-induced epileptiform activity in rat hippocampal-entorhinal cortex slices. 1246 May 49

Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl2 x 6H2O (1%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/- 0.10; IDV+NF, 1.94 +/- 0.07 vs IDV, 1.15 +/- 0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/- 0.09; IDV+NF, 7.63 +/- 0.14 vs IDV, 6.17 +/- 0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/- 0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/- 0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity.
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PMID:Vasodilator agents protect against indinavir nephrotoxicity. 1451 98


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