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)

Thrombin, the central regulatory enzyme in coagulation, when incubated in nanomolar concentrations with murine neuroblastoma cells produced a rapid and marked increase in tritiated guanosine 3',5'-monophosphate (cyclic GMP) formation that was blocked by hirudin and competitively antagonized by dansylarginine N-(3-ethyl-1,5-pentanediyl)amide. Diisopropylphosphofluoridate-inactivated thrombin as well as the serine protease trypsin were markedly less potent and less effective than alpha-thrombin in producing this effect. Thrombin-stimulated cyclic GMP formation was inhibited by mepacrine and nordihydroguaiaretic acid but unaffected by indomethacin, suggesting that lipoxygenase metabolites of arachidonic acid are involved in the response. These results suggest that a thrombin-like protease in the brain may be involved with the function of neurons or that thrombin interactions with nerve cells, such as those following cerebral hemorrhage or other trauma of the central nervous system, may be important in the subsequent neuropathology.
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PMID:Thrombin stimulation of guanosine 3',5'-monophosphate formation in murine neuroblastoma cells (clone N1E-115). 630 70

The nonapeptide, bradykinin, elevated the level of cyclic GMP in two neural cell lines, neuroblastoma X glioma hybrid cells (clone 108CC15) and glioma cells (clone C6-4-2). In the hybrid cells the half-maximal stimulation occurred at 0.1 nM and the maximum was reached at 10 nM bradykinin. As soon as 30 s after the addition of bradykinin to the cultured cells, the intracellular concentration of cyclic GMP had increased maximally. The subsequent decline to the original level proceeded more slowly and lasted around 10 min. Hybrid cells incubated for 10 min in the presence of bradykinin and washed thereafter, did not respond at all to a subsequent 1 min challenge incubation with bradykinin. This nearly complete desensitization lasted for a period of 20 min. One hour after removal of bradykinin the original response to the peptide was restored. Modified and partial sequences of bradykinin were also investigated for their ability to induce the cyclic GMP response in the hybrid cells. Removal of amino acids from either terminus of bradykinin led to an almost complete loss of activity. The data are discussed with respect to our previous observation that bradykinin causes a slow hyperpolarization response in these cell lines and that on prolonged exposure to the peptide the membrane potential response of the cells is lost due to desensitization.
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PMID:Bradykinin regulates the level of guanosine 3',5'-cyclic monophosphate (cyclic GMP) in neural cell lines. 631 12

Serotonin has been previously shown to stimulate palate reorientation. To elucidate the mechanism by which the neurotransmitter may be regulating palate morphogenesis, the effects of serotonin on cell motility and various metabolic reactions have been measured in vitro. To monitor cell motility, a chemotactic system was employed in which cultured palate mesenchymal cells in a modified Boyden chamber migrate toward the chemoattractant(s) in N-18 neuroblastoma conditioned medium. Serotonin stimulated cell motility and 10(-5) M was optimal with nearly 100% stimulation achieved. With N-18 conditioned medium diluted 1:100, serotonin stimulated cell motility 4.9-fold. Serotonin itself was not chemotactic but modulated cell movement in the presence of the chemoattractant. Protein carboxyl methylation was stimulated by serotonin about 100% at concentrations ranging from 3 X 10(-7) M to 3 X 10(-6) M in different experiments. The net stimulation may have been elicited by an indirect effect since serotonin also inhibited demethylation of protein methyl esters. Serotonin was shown to inhibit cyclic AMP in cultured palate cells: 10(-5) M agonist depressed levels to 19% of control in 3 h. Further, prostaglandin E1, which stimulated cyclic AMP levels, markedly inhibited cell motility in the chemotactic assay. Thus there is an inverse relationship between cyclic AMP levels and cell motility in fetal palate cells. Finally it was observed that serotonin stimulated cyclic GMP levels; 10(-5) M serotonin optimally stimulated cyclic GMP with a spike of stimulation (6.1-fold) within 30 sec. In summary, serotonin in palate cells stimulates both protein carboxyl methylation and cyclic GMP. Modulation of these reactions could be regulating cell motility and/or protein secretion, which in turn could function in palate reorientation.
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PMID:Serotonin regulation of palatal cell motility and metabolism. 631 57

Preincubation of murine neuroblastoma cells (clone N1E-115) with terbium chloride resulted in a significant potentiation of carbachol-mediated increase in cyclic GMP formation. This effect was accompanied by a shift of the peak response from 30 s to 120 s and a 6-fold decrease in carbachol concentration producing half-maximal responses, in addition to a significant increase in the Hill coefficient. Terbium ions also caused a significant decrease in the affinity and an increase in the maximum binding of [3H]quinuclidinyl benzilate to muscarinic receptors, the change in affinity being mainly due to a decrease in the association rate. Preincubation of cells with 1 mM carbachol for 4 h (the desensitized state of the muscarinic receptor) resulted in a decrease in the ability of terbium to alter [3H]quinuclidinyl benzilate binding. The effects of terbium reported here might be due to its affecting muscarinic receptor-effector coupling, which is considered to be lost upon receptor desensitization.
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PMID:Kinetic effects of terbium ions on muscarinic acetylcholine receptors of murine neuroblastoma cells. 631 10

In neuroblastoma N1E 115 cells, carbachol, histamine and PGE1 elevated cyclic GMP content and, induced the efflux of preloaded 45Ca2+, the release of membrane-bound Ca2+ measured by fluorescent CTC, and the increase in [Ca2+]i as measured by Quin 2 fluorescence. The time course of the responses, the absolute requirement of extracellular Ca2+, the inhibition by receptor blockers, and the concentration dependency on histamine were all similar between these responses. The observation indicates that the mobilization of Ca2+, especially the increase of [Ca2+]i, may be intimately linked to the synthesis of cyclic GMP in the cells.
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PMID:Receptor-mediated regulation of calcium mobilization and cyclic GMP synthesis in neuroblastoma cells. 633 50

Thrombin, a serine protease that regulates hemostasis, has been shown to stimulate the formation of cGMP in murine neuroblastoma cells. The nervous system in vivo thus may be postulated to respond to this blood-borne factor after it breaches the blood-brain barrier, as in trauma. Human alpha-thrombin was radiolabeled with 125I and shown to bind rapidly, reversibly, and with high affinity to human brain and spinal cord. These findings indicate the presence of specific thrombin-binding sites in nervous tissue and may have important clinical implications.
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PMID:Thrombin binding to human brain and spinal cord. 664 28

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

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

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


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