UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary protein independently modulates albuminuria (U(Alb)V) and albumin synthesis (AlbSyn) in nephrotic rats. While some amino acids are without effect on renal hemodynamics, arginine (Arg) augments renal blood flow and glomerular filtration rate, increases AlbSyn in tissue culture and isolated perfused livers, and could be one specific amino acid causing both decreased glomerular permselectivity and increased AlbSyn. Nephrotic rats were fed 10% casein (LP); 30% casein (HP); 30% casein with the inhibitor of nitric oxide (NO) synthesis N omega-nitro-L-arginine methyl ester (HP + L-NAME); 10% casein supplemented with Arg and amino acids that are Arg precursors of or are derived from Arg (proline, glutamate, and aspartate) in an amount in the increment between 10 and 30% casein (ArgAA); ArgAA supplemented with NH4 acetate to provide a diet isonitrogenous to 30% casein (ArgAA + NH4); or 10% casein plus an incomplete mixture of amino acids (Inc) containing the increment in histidine, phenylalanine, tryptophan, tyrosine, lysine, glycine, alanine, serine, threonine, cysteine, and methionine provided when the diet was changed from 10 to 30% casein. U(Alb)V increased significantly in HP and by a significantly greater amount in HP + L-NAME, but did not change in LP, ArgAA, or ArgAA + NH4. U(Alb)V tended to increase in Inc, was significantly greater than in LP or in ArgAA + NH4, but less than in HP. AlbSyn ([3H]phenylalanine incorporation) was no different in Inc than in HP, and was significantly greater than in either ArgAA + NH4 or LP. Increased AlbSyn results from increased ingestion of one or more of amino acids in Inc, but not from Arg or its precursors or products or from total dietary nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine augments neither albuminuria nor albumin synthesis caused by high-protein diets in nephrosis. 144 79

The ability of five agents (dizocilpine [MK-801], 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline [NBQX], enadoline [CI-977], L-nitroarginine methyl ester [L-NAME] and BW 1003c87) with well defined, distinct pharmacological profiles and with established anti-ischemic efficacy, to modify neuronal damage has been examined in a simple in vivo model of glutamate excitotoxicity. Cortical lesions were produced in physiologically-monitored halothane-anesthetised rats by reverse dialysis of glutamate. The volume of the lesion was quantified histologically by image analysis of approximately 20 sections taken at 200 microm intervals throughout the lesion. The AMPA and NMDA receptor antagonists (NBQX and MK-801) and the inhibitor of nitric oxide synthase (L-NAME) significantly reduced the lesion volume by a similar extent (by approximately 30% from vehicle). Two agents (the kappa opioid agonist, CI-977 and the sodium channel blocker, BW 1003c87) which putatively inhibit the release of endogenous glutamate presynaptically, had dissimilar effects on lesion size. CI-977 failed to alter the amount of damage produced by exogenous glutamate, whereas BW 1003c87 reduced the lesion size by approximately 50%. Using this model, the neuroprotective effects of anti-ischemic drugs can be explored in vivo, uncomplicated in contrast to experimental ischemia by reduced oxygen delivery, drug effects on tissue blood flow and compromised energy generation. In consequence, additional mechanistic insight into anti-ischemic drug action in vivo can be obtained.
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PMID:Pharmacological modification of glutamate neurotoxicity in vivo. 750 85

1. Glutamate inhibits the electrically evoked release of noradrenaline in rabbit brain cortex slices; the inhibition is mediated by adenyl compounds, presumably adenosine. The aim of the present study was to identify the receptors involved in this indirect inhibitory effect of glutamate. Slices of the occipitoparietal cortex were preincubated with [3H]-noradrenaline and then superfused and stimulated by trains of 6 pulses, 100 Hz. 2. The ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AM-PA; 10-100 microM), kainate (10-100 microM) and N-methyl-D-aspartate (NMDA; 30-300 microM) but not the metabotropic glutamate receptor agonist, 1-amino-1,3-cyclopentanedicarboxylate (ACPD; 10-100 microM) reduced the electrically evoked overflow of tritium. 3. The effects of AMPA, kainate and NMDA were attenuated or abolished by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine deaminase but not by the alpha 2-adrenoceptor antagonist yohimbine, the gamma-aminobutyric acid (GABA) receptor antagonists, bicuculline and 2-hydroxysaclofen and the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 4. The NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5) blocked the inhibitory effect of NMDA but not that of AMPA and kainate. The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the effect of AMPA but not of kainate and NMDA. 5. In addition to decreasing the electrically evoked overflow of tritium, AMPA, kainate and NMDA but not ACPD caused a steep but transient rise of basal tritium efflux. This immediate releasing effect was not significantly changed by DPCPX, adenosine deaminase, yohimbine, bicuculline, 2-hydroxysaclofen and L-NAME (except that L-NAME enhanced the effect of kainate). AP5 and CNQX antagonized the immediate releasing effects in the same way that they antagonized the inhibition by AMPA, kainate and NMDA of the electrically evoked overflow of tritium.6. It is concluded that AMPA, kainate and NMDA, like glutamate, reduce the electrically evoked release of noradrenaline by releasing adenosine or an adenine nucleotide which is then degraded to adenosine. Activation of each of the three ionotropic glutamate receptors, AMPA, kainate and NMDA receptors, but not activation of metabotropic glutamate receptors can initiate this indirect inhibitory effect on the release of noradrenaline (as well as the known noradrenaline releasing effect).
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PMID:Ionotropic glutamate receptor types leading to adenosine-mediated inhibition of electrically evoked [3H]-noradrenaline release in rabbit brain cortex slices. 750 27

Repeated administration of cocaine to animals results in sensitization to several reactions to the drug, including seizures and mortality. These consequences are thought to be related to the pathology that develops in humans abusing cocaine. Previous studies implied the involvement of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in cocaine-induced toxicity, and recent studies documented a role for nitric oxide in NMDA-receptor mediated neurotoxicity. The present study was undertaken to determine whether nitric oxide synthase inhibitors block the development of sensitization to the toxic effects of cocaine in mice. Repeated administration of cocaine (45 mg/kg/day; intraperitoneally) to Swiss Webster mice, for 7 days, resulted in a progressive increase in the duration of the convulsive response to cocaine, an increase in the number of animals that had seizures, and augmentation in lethality rate. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day; intraperitoneally) or NG-nitro-L-arginine (NO-Arg; 25 mg/kg/day; intraperitoneally) completely abolished the sensitization to the convulsive and lethal responses to cocaine. Receptor binding assays indicated first, that pretreatment with L-NAME apparently diminished cocaine-induced upregulation of cortical NMDA receptors, and second, that the effects of the nitric oxide synthase inhibitors tested are not mediated via a direct interaction of the drugs with the phencyclidine/NMDA receptor complex. Taken together, the present study suggests an important role for nitric oxide in the development of sensitization to the toxic effects of cocaine, and further supports the relationship between NMDA-receptor mediated neurotoxicity and nitric oxide.
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PMID:Blockade of sensitization to the toxic effects of cocaine in mice by nitric oxide synthase inhibitors. 751 59

Excitatory amino acid (EAA) receptors such as N-methyl-D-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-L-arginine methylester (L-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. L-arginine but not D-arginine caused a phase delay, and L-NAME blocked L-arginine-induced phase delay. In addition, cotreatment with NMDA and L-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.
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PMID:Effects of nitric oxide synthase inhibitors on N-methyl-D-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro. 751 62

The accumulation of extracellular glutamate and aspartate in the striatum of rats during ischaemia was examined by perfusion with Ca(+)-free medium and treatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Male Wistar rats were subjected to 30 min ischaemia using the 4-vessel occlusion model or high K(+)-depolarization. Extracellular glutamate and aspartate were monitored by in vivo microdialysis. Perfusion with Ca(2+)-free medium and systemic administration or local perfusion of L-NAME reduced the K(+)-evoked glutamate accumulation but not the ischaemia-induced glutamate accumulation. The aspartate concentration was unaffected in both conditions. Our data suggest that the extracellular glutamate and aspartate originates from a Ca(2+)-independent pool during forebrain ischaemia and is not modulated by nitric oxide. In high K(+)-depolarization the accumulated glutamate may arise, at least in part, from enhanced vesicular release and is modulated by nitric oxide.
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PMID:L-NAME modulates glutamate accumulation induced by K(+)-depolarization but not by forebrain ischaemia in the rat striatum. 752 79

The contribution of the intracellular messengers nitric oxide, arachidonic acid and protein kinase C to persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin injury-induced nociceptive behaviours were reduced by intrathecal pretreatment with inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester, L-NAME), arachidonic acid (dexamethasone) or protein kinase C [protein kinase C (19-26) and 1-95-(isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride, H-7]. Each of these agents affected the tonic, but not the acute, phase of the formalin response. Furthermore, none of these agents affected mechanical or thermal flexion reflex thresholds in rats not injected with formalin. Conversely, formalin-induced nociceptive responses were enhanced by stimulators of nitric oxide (sodium nitroprusside), arachidonic acid metabolism (arachidonic acid) or protein kinase C [(+/-)-1-oleoyl-2-acetyl-glycerol], and were slightly reduced by inositol trisphosphate. Mechanical flexion reflexes were also reduced by arachidonic acid, while thermal flexion reflexes were reduced after treatment with sodium nitroprusside, arachidonic acid or [(+/-)-1-oleoyl-2-acetyl-glycerol]. The enhancement of formalin nociceptive behaviours (hyperalgesia) in rats treated with L-glutamate or substance P was reversed by pretreatment with inhibitors of nitric oxide (L-NAME), arachidonic acid (dexamethasone) or protein kinase C (H-7). The results suggest that central sensitization and persistent nociception following formalin-induced tissue injury, and the hyperalgesia in the formalin test induced by L-glutamate and substance P, are dependent on the intracellular messengers nitric oxide, arachidonic acid and protein kinase C.
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PMID:Intracellular messengers contributing to persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model. 752 41

The ability of glutamate to stimulate generation of intracellular oxidant species was determined by microfluorescence in cerebellar granule cells loaded with the oxidant-sensitive fluorescent dye 2,7-dichlorofluorescin (DCF). Exposure of cells to glutamate (10 microM) produced a rapid generation of oxidants that was blocked approximately 70% by MK-801 (a noncompetitive NMDA-receptor antagonist). To determine if nitric oxide (NO) or reactive oxygen species (ROS) contributed to the oxidation of DCF, cells were treated with compounds that altered their generation. NO production was inhibited with NG-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) and reduced hemoglobin (NO scavenger). Alternatively, cells were incubated with superoxide dismutase (SOD) and catalase, which selectively metabolize O2-. and H2O2. Concurrent inhibition of O2-. and NO production nearly abolished intracellular oxidant generation. Pretreatment of cells with either chelerythrine (1 microM, protein kinase C inhibitor) or quinacrine (5 microM, phospholipase A2 inhibitor) before addition of glutamate also blocked oxidation of DCF. Generation of oxidants by glutamate was significantly reduced by incubating the cells of Ca(2+)-free buffer. In cytotoxicity studies, a positive correlation was observed between glutamate-induced death and oxidant generation. Glutamate-induced cytotoxicity was blocked by MK-801 and attenuated by treatment with L-NAME, chelerythrine, SOD, or quinacrine. It is concluded that glutamate induces concurrent generation of NO and ROS by activation of both NMDA receptors and non-NMDA receptors through a Ca(2+)-mediated process. Activation of NO synthase and phospholipase A2 contribute significantly to this response. It is proposed that simultaneous generation of NO and ROS results in formation of peroxynitrite, which initiates the cellular damage.
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PMID:NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species: implication for cell death. 759 85

It has been suggested that nitric oxide (NO) interferes with both glutamatergic neurotransmission and the regulation of cerebral blood flow in epileptic seizures. This study examines the effect of an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), on the extracellular concentration of glutamate during seizures induced by kainic acid (KA; 10 mg/kg), both drugs being administered systemically. L-NAME was injected 40 min before KA. The extracellular glutamate concentration was measured in the hippocampus of awake, spontaneously breathing rats using microdialysis combined with HPLC. The arterial blood gases and glycemia were periodically checked. The arterial blood pressure, the electrocorticogram and the body temperature were continuously monitored. In basal conditions, the systemic injection of L-NAME increased arterial blood pressure but did not significantly change the hippocampal glutamate level. In seizure conditions, the hippocampal glutamate concentration was either slightly increased or not significantly changed in saline-treated rats (n = 6) but it was decreased in L-NAME-treated rats (n = 6). At all times after KA injection, the hippocampal glutamate concentration was significantly lower in L-NAME-treated rats than in saline-treated rats. Unlike saline-treated rats, L-NAME-treated rats died during status epilepticus. This study shows that acute systemic injection of L-NAME reduces the extracellular concentration of glutamate in the rat hippocampus during seizures induced by KA.
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PMID:Effect of inhibiting NO synthesis on hippocampal extracellular glutamate concentration in seizures induced by kainic acid. 760 44

To study the sequence of degenerative events possibly associated with cholinergic cell death in Alzheimer's disease, septal cholinergic neurons derived from rat embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts of choline acetyltransferase (ChAT)-immunopositive neurons and measurement of ChAT activity revealed that concentrations of glutamate on the order of 70 microM killed 50% of cholinergic neurons after 24 hr of treatment. Neurotoxic effects were not aimed at cholinergic neurons specifically, since other populations of cells present in these cultures were also affected at similar concentrations. The noncompetitive N-methyl-D-aspartate (NMDA) receptor channel antagonist MK-801 (10 microM) abolished acute neuronal swelling and rescued from late degeneration both cholinergic and noncholinergic cells when concentrations of glutamate up to 500 microM were added to the cultures. Protective effects declined progressively with increasing concentrations of the amino acid, even when MK-801 was raised to its highest nontoxic levels, e.g., 50 microM. the kainate/quisqualate receptor antagonist CNQX provided no protection alone or in combination with MK-801. Nerve growth factor (NGF), used in standard culture conditions to stimulate the expression of the cholinergic phenotype, was shown not to influence excitotoxic neurodegenerative changes. Several observations suggested that nitric oxide (NO) may act as an intercellular messenger of NMDA-mediated cell death in septal cultures: 1) Most of the cholinergic neurons contained the NO synthase enzyme as characterized by NADPH-diaphorase (NADPH-d) staining; 2) sodium nitroprusside (SNP) [a chemical with the ability of generating NO] was capable of mimicking some of the aspects of the glutamate-induced degenerative process; 3) the rise in cyclic GMP which was observed in the presence of toxic levels of glutamate and which is usually taken as an index of NO production, was antagonized by MK-801 and by the inhibitor of the NO synthase enzyme, L-NOARG. Yet, the fact that L-NOARG and its congener, L-NAME, were ineffective in preventing glutamate-induced neurodegenerative changes in our culture system did not substantiate our working hypothesis. Altogether these results suggest that glutamate-induced cholinergic neuronal death is the consequence of an overstimulation of NMDA receptors and that neither NGF nor NO plays a key role in the degenerative process.
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PMID:Death of septal cholinergic neurons produced by chronic exposure to glutamate is prevented by the noncompetitive NMDA receptor/channel antagonist, MK-801: role of nerve growth factor and nitric oxide. 762 90

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