Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The coupling of m5 muscarinic acetylcholine receptors to the generation and release of nitric oxide (NO) was investigated. Chinese hamster ovary cells, which stably express m5 receptors, were transiently transfected with the gene encoding neuronal NO synthase and used as a model system. Increased generation of NO upon stimulation of cells by muscarinic agonists was detected by an increase in cyclic GMP in admixed mouse neuroblastoma N1E-115 cells or more directly by measuring the conversion of L-arginine into L-citrulline. Carbachol increased cyclic GMP formation in the mixture of cells in a time- and concentration-dependent manner, with a half-maximal response occurring in the nanomolar range. This response was significantly attenuated by scavengers of NO or inhibitors of NO synthase. This high potency of carbachol was also observed in measurements of L-citrulline formation. A series of muscarinic agonists were as efficacious as carbachol in stimulating NO synthase, whereas McN-A-343 and pilocarpine were partial agonists in this regard. Evidence for an exceptionally high efficiency of coupling of m5 receptors to this response and its possible implication in the interaction between cholinergic and dopaminergic neurotransmission is discussed.
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PMID:Efficient coupling of m5 muscarinic acetylcholine receptors to activation of nitric oxide synthase. 750 88

There is rapidly accumulating evidence that generation of nitric oxide (NO) through a Ca2+ and calmodulin-dependent pathway plays various important roles in the central nervous system. In the present study, effects of several antipsychotics on the activity of NO synthase were investigated in rat cerebellum and neuroblastoma N1E-115 cells, due to the known ability of these agents to inhibit calmodulin. In cytosolic preparations of rat cerebellum, the antipsychotic drugs inhibited the conversion of [3H]L-arginine into [3H]L-citrulline by NO synthase in a concentration-dependent manner. This inhibition was noncompetitive in nature, and it exhibited an excellent correlation with blockade of calmodulin activity. Furthermore, these drugs attenuated cyclic GMP formation induced by a calcium ionophore in N1E-115 cells, a response which takes place as a consequence of NO generation. Taken together, our data demonstrate that antipsychotic drugs inhibit NO formation in vitro. It is unlikely, however, that these actions might contribute to their therapeutic and/or side effects, since they take place at relatively high concentrations.
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PMID:Inhibition of neuronal nitric oxide synthase by antipsychotic drugs. 753 51

Inhibitory effects of nitric oxide (NO) on vesicular stomatitis virus (VSV) infection were investigated by using a VSV-susceptible mouse neuroblastoma cell line, NB41A3. Productive VSV infection of NB41A3 cells was significantly inhibited by an organic NO donor, S-nitro-N-acetylpenicillamine (SNAP), while the control compound N-acetylpenicillamine (NAP) had no effect. Survival rate of VSV-infected cells was greatly increased by the treatment with SNAP, while the NAP treatment did not have any effect. Adding SNAP 30 min prior to infection resulted in complete inhibition of viral production when a low multiplicity of infection (MOI) was used. Substantial inhibition of viral production was also obtained with treating cells 6 h earlier before infection with a higher MOI. Activating the neuronal NO synthase by treating cells with N-methyl-D-aspartate (NMDA) led to significant inhibition of viral production by cells infected at the three doses of virus tested (MOIs of 0.1, 1, and 5). The inhibitory effect of NMDA on viral infection was totally blocked by the NO synthase inhibitor N-methyl-L-arginine. However, adding hemoglobin, a strong NO-binding protein and thus an inactivator of NO activity, did not reverse the NMDA-induced inhibition of viral production, suggesting that NO might exert its antiviral effects inside the NO-producing cells. Collectively, these data support the anti-VSV effects of NO, which might be one of the important factors of natural immunity in controlling the initial stages of VSV infection in the central nervous system.
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PMID:Inhibition of vesicular stomatitis virus infection by nitric oxide. 753 52

In the present study we investigated uptake of the nitric oxide (NO) synthase inhibitors NG-methyl-L-arginine and NG-nitro-L-arginine by the mouse neuroblastoma x rat glioma hybrid cell line NG108-15. Uptake of NG-methyl-L-arginine was characterized by biphasic kinetics (Km1 = 8 mumol/L, Vmax1 = 0.09 nmol x mg-1 x min-1; Km2 = 229 mumol/L, Vmax2 = 2.9 nmol x mg-1 x min-1) and was inhibited by basic but not by neutral amino acids. Uptake of NG-nitro-L-arginine followed Michaelis-Menten kinetics (Km = 265 mumol/L, Vmax = 12.8 +/- 0.86 nmol x mg-1 x min-1) and was selectively inhibited by aromatic and branched chain amino acids. Further characterization of the transport systems revealed that uptake of NG-methyl-L-arginine is mediated by system y+, whereas systems L and T account for the transport of NG-nitro-L-arginine. In agreement with these data on uptake of the inhibitors, L-lysine and L-ornithine antagonized the inhibitory effects of NG-methyl-L-arginine on bradykinin-induced intracellular cyclic GMP accumulation, whereas L-tryptophan, L-phenylalanine, and L-leucine interfered with the effects of NG-nitro-L-arginine. These data suggest that rates of uptake are limiting for the biological effects of NO synthase inhibitors.
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PMID:Characterization of neuronal amino acid transporters: uptake of nitric oxide synthase inhibitors and implication for their biological effects. 753 32

It has been shown that nitric oxide (NO) regulates NO synthase (NOS) activity through negative feedback in cytosolic enzyme preparations in various cell types. We compared the effects of the NO-generating compounds S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) on NOS activity in intact neuroblastoma N1E-115 cells and in the cytosol obtained from the same cells. Enzyme activity was measured by the conversion of L-[3H]arginine into L-[3H]citrulline. At concentrations that elicit almost complete inhibition of NOS activity in cytosolic enzyme preparations of these cells, SIN-1 and SNP did not cause significant attenuation of enzyme activity measured at 45 min in intact cells. It is surprising that SIN-1 and SNP markedly stimulated L-[3H]citrulline formation in a time- and concentration-dependent manner when cells were incubated with the compounds for > 1.5 h. Neither inhibitory nor stimulatory effects of SNAP on NOS were observed in intact N1E-115 cells. This is in contrast to the inhibitory effects of SNAP in cytosolic preparations of the enzyme. The increased NOS activity by SIN-1 or SNP in intact cells was dependent on the presence of extracellular Ca2+, suggesting that it might be due to increased Ca2+ influx. On the other hand, measurements of the activity of lactate dehydrogenase showed that there was no generalized increase in cell permeability in response to SIN-1 or SNP. There was no agreement in the rank order of potencies of these compounds in activating guanylate cyclase and in affecting NOS activity, both in broken-cell preparations and in intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anomalous increase in nitric oxide synthase activity by certain nitric oxide-generating compounds in intact neuronal cells. 754 Jun 59

We examined the effects of endogenous basic proteins rich in the amino acid L-arginine on neuronal NO synthase activity by monitoring cyclic GMP formation in intact neuron-like neuroblastoma N1E-115 cells. Histone, protamine and myelin basic protein significantly stimulated cyclic GMP formation, both in a time- and concentration-dependent manner. These effects were blocked by hemoglobin and NO synthase inhibitors. Removal of the extracellular/intracellular Ca2+ gradient by a Ca2+ chelator completely abolished the cyclic GMP responses elicited by histone and protamine, suggesting that influx of extracellular Ca2+ might be involved in their activation of NO synthase. The effects of myelin basic protein on cyclic GMP formation, however, appeared to be due to Ca2+ release from intracellular stores. In cytosolic preparations of rat cerebellum, these basic proteins inhibited the metabolism of L-arginine into L-citrulline by NO synthase. We conclude from our findings that endogenous basic proteins might be involved in the regulation of neuronal NO synthase activity. Their effects on the enzyme could be either stimulatory or inhibitory, depending on whether the basic proteins exert their effects extracellularly or intracellularly, respectively.
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PMID:Regulation of neuronal nitric oxide synthase by histone, protamine, and myelin basic protein. 754 48

The molecular events associated with beta-amyloid-induced neuronal injury remain incompletely characterized. Using a substantia nigra/neuroblastoma hybrid cell line (MES 23.5) synthetic beta-amyloid 1-40 induced a time and dose-dependent apoptotic cell death which was characterized by cell shrinkage and fragmentation of DNA, and was inhibited by aurintricarboxylic acid (ATA), and cycloheximide (CHX). Following beta-amyloid 1-40 treatment, cyclic GMP, an index of NO synthesis, was increased in MES 23.5 cells. The NO scavenger hemoglobin, as well as the NO synthase inhibitors NG-monomethyl-L-arginine acetate (L-NMMA) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NI0) attenuated such increases. These same inhibitors and scavengers also significantly prevented cytotoxicity. beta-Amyloid also induced an early and transient increase in intracellular calcium as monitored with laser scanning confocal microscopy and Fluo-3 imaging. These induced calcium transients could be significantly blocked by the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801. Pretreatment with MK-801 or removal of extracellular Ca2+ also reduced beta-amyloid-induced NO production and neurotoxicity. Furthermore, beta-amyloid neurotoxicity was greatly enhanced in the absence of Mg2+ or in the presence of glutamate or NMDA. These data suggest that beta-amyloid can lead to apoptotic cell death through a NO mediated process possibly triggered by Ca2+ entry through activated NMDA-gated channels.
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PMID:Cell death induced by beta-amyloid 1-40 in MES 23.5 hybrid clone: the role of nitric oxide and NMDA-gated channel activation leading to apoptosis. 758 71

NADPH diaphorase activity is used as a histochemical marker for neuronal nitric oxide (NO) synthase; however, it remains unclear whether these activities are directly correlated in all tissues. In N1E-115 neuroblastoma cells, NADPH diaphorase activity was found primarily in the particulate fraction, whereas NO synthase activity was mostly soluble. Non-induced macrophages expressed significant NADPH diaphorase activity (which was mostly particulate) but virtually no NO synthase activity. Induction of macrophages produced marked increases in both NO synthase and NADPH diaphorase activities in the soluble and particulate fractions. In endothelial cells, both NO synthase and NADPH diaphorase activities were found mostly in the particulate fraction. Purified NO synthases from brain (type I), macrophages (type II), and endothelium (type III) all showed NADPH diaphorase activity; relative activities were: macrophage > endothelium > brain. These data indicate that all known NO synthases are NADPH diaphorases; however, NO synthases represent only a fraction of total cellular NADPH diaphorase activity and these activities are not always co-localized.
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PMID:Nitric oxide synthases in neuronal cells, macrophages and endothelium are NADPH diaphorases, but represent only a fraction of total cellular NADPH diaphorase activity. 769 May 49

We investigated the effects of lithium ion (Li+) on muscarinic receptor-mediated nitric oxide (NO) generation, and guanylate cyclase (GCase) activation using the mouse neuroblastoma clone, N1E-115. The levels of released NO were determined by measuring the levels of nitrite/nitrate in the incubation medium, and the activity of GCase was measured with an assay for cellular cyclic [3H] GMP levels. We determined that Li+ had no effects on muscarinic receptor-activated elevation of nitrite/nitrate levels, which were significantly inhibited by 100 microM L-NG-monomethylarginine, although it has been reported that Li+ inhibits muscarinic receptor-activated cyclic GMP formation in the cells. In addition, Li+ inhibited the cyclic GMP formation induced by an NO donor, sodium nitroprusside (SNP), in both intact cells and a crude cellular homogenate; thus, the inhibition by Li+ of muscarinic receptor-mediated cyclic GMP synthesis appeared to be at the level of GCase, but not NO synthase.
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PMID:Inhibition by lithium of cyclic GMP formation without inhibition of nitric oxide generation in the mouse neuroblastoma cell (N1E-115). 784 Aug 63

Effects of the calmodulin inhibitor calmidazolium on stimulation of nitric oxide (NO) release were investigated in neuroblastoma N1E-115 cells. NO release was determined indirectly by measuring cyclic GMP formation. Instead of the expected decrease in NO generation based on the calmodulin dependence of neuronal NO synthase, calmidazoline paradoxically increased cyclic GMP formation. Maximal activation occurred at 3 min and the effects were concentration dependent. This calmidazolium-stimulated NO release was markedly blocked by hemoglobin and N-monomethyl-L-arginine.
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PMID:The calmodulin antagonist calmidazolium stimulates release of nitric oxide in neuroblastoma N1E-115 cells. 838 25


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