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: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylate cyclase (EC 4.6.1.1) activity was stimulated by low concentrations of dopamine and apomorphine, but not by low concentrations of norepinephrine in homogenates of malignant mouse neuroblastoma cells. In cyclic AMP-induced "differentiated" cells, dopamine concentration required for a maximal increase in adenylate cyclase activity was about 10-fold less than that required for a similar increase in control cells, and norepinephrine-sensitive adenylate cyclase activity became apparent at low norepinephrine concentrations. The pharmacological properties of dopamine-sensitive adenylate cyclase were different from those of norepinephrine-sensitive enzyme. For example, dopamine-stimulated adenylate cyclase activity was markedly reduced by low concentrations of haloperidol and phentolamine, whereas norepinephrine-stimulated enzyme activity required higher concentrations of these blocking agents for a similar amount of inhibition. Norepinephrine-stimulated enzyme activity was markedly blocked by low concentrations of propranolol, whereas dopamine-stimulated enzyme activity required a much higher concentration of this blocking agent for a similar amount of inhibition. Low concentrations of isoproterenol increased adenylate cyclase activity in malignant cells, but in "differentiated" cells even a high concentration failed to do so. The fact that dopamine and norepinephrine produced an additive stimulatory effect on adenylate cyclase activity suggests that they interact at different receptor sites. This suggestion is further supported by the observation that the combination of prostaglandin E(1) and norepinephrine produced an additive stimulatory effect of enzyme activity. The observation that the effects of dopamine and prostaglandin E(1) are not additive, coupled with the observation that a low concentration of phentolamine blocked the effect of prostaglandin E(1), suggests that these two agents may interact at a common site.
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PMID:Demonstration of dopamine-sensitive adenylate cyclase in malignant neuroblastoma cells and change in sensitivity of adenylate cyclase to catecholamines in "differentiated" cells. 436 72

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

We describe a child with a localised pelvic neuroblastoma and a hypertensive crisis during the first weeks of life due to elevated systemic norepinephrine of tumoural origin. In spite of treatment with high doses of alpha-blockers, blood pressure did not respond fully and the boy had a very unstable circulation. Surgery was performed at one month of age. Adenosine, a potent short-acting vasodilator, was used for peroperative blood pressure control to protect the patient from an uncontrolled hypertensive crisis. During tumour manipulation the child became hypertensive with systolic pressure exceeding 130 mm Hg and adenosine infusion (100 micrograms.kg-1.min-1) was started with a prompt normalisation of the blood pressure. Adenosine infusion could be discontinued after tumour removal. Norepinephrine, dopamine, homovanillic acid and vanillylmandelic acid in urine were elevated preoperatively and normalised at follow up. Plasma concentrations of norepinephrine and dopamine were elevated preoperatively. Norepinephrine increased during hypertension due to tumour manipulation. Plasma neuropeptide Y increased during tumour manipulation but still within the normal range for infants. It is concluded that adenosine can be used peroperatively in children with severe hypertension and in this case no adverse effects of adenosine were noted. Furthermore, tumour synthesis and systemic release of norepinephrine, but not neuropeptide Y, contributed to hypertension in this child with neuroblastoma.
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PMID:Adenosine for per-operative blood pressure control in an infant with neuroblastoma. 757 24

Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.
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PMID:Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression. 757 74

This paper describes the establishment of a new polyclonal human neuroblastoma cell line NAL-GT. Pharmacological characterisation of a cell line comprising > 70% neurones using radioligand binding, Ins(1,4,5)trisphosphate (Ins(1,4,5)P3) mass formation, intracellular Ca2+ ([Ca2+]i) determinations and cyclic adenosine monophosphate (cAMP) formation has been performed. Carbachol (1 mM) and noradrenaline (10 microM) increased Ins(1,4,5)P3 formation 2-3-fold basal. Noradrenaline (10 microM) and morphine (10 microM) reduced forskolin stimulated cAMP formation by 19.7 and 30.5%, respectively. Carbachol (1 mM) and K+ (50 mM) increased [Ca2+]i. These data indicate that polyclonal (heterogeneous) NAL-GT cells express muscarinic, alpha 1 and alpha 2 adrenoceptors, opioid receptors and voltage-sensitive Ca2+ channels and may prove useful in the study of the cellular basis of drug action.
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PMID:Characterisation of a new human neuroblastoma cell line, NAL-GT. 774 83

Meta-[211At]astatobenzylguanidine ([211At]MABG) is an astatinated analogue of meta-iodobenzylguanidine (MIBG) that could be of value for therapeutic applications. The initial goal of this study was to determine whether [211At]MABG is taken up, like MIBG, by a specific uptake-I mechanism. Norepinephrine and desipramine (DMI) decreased [211At]MABG uptake in SK-N-SH human neuroblastoma cells. This uptake was found to be energy-dependent: In mice, pre-treatment with DMI reduced uptake of [211At]MABG at 1 hr post-injection in the adrenal and in the heart. Tetrabenazine at a dose of 40 mg/kg reduced uptake of [211At]MABG in the mouse heart in vivo (69% of control) whereas up to 100 microM of tetrabenazine did not affect the in vitro uptake of [211At]MABG in SK-N-SH cells. In SK-N-SH cells, 53% and 38%, respectively, of the initial uptake of [211At]MABG was retained at 4 hr and 6 hr. For no-carrier-added (n.c.a.) [131I]MIBG these values were similar, 60% and 48%. The ability of SK-N-SH cells to incorporate [3H]thymidine was reduced to less than 50% of control values when treated with as little as 3.2 nCi of [211At]MABG. In contrast, no significant reduction in the thymidine uptake was observed, even with 80 nCi of n.c.a. MIBG.
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PMID:Meta-[211At]astatobenzylguanidine: further evaluation of a potential therapeutic agent. 820 83

We compared the alpha 1-adrenergic receptor subtypes in two neuronal cell lines, SK-N-MC (human neuroepithelioma) and NB41A3 (murine neuroblastoma). 125I-BE 2254 labeled alpha 1-adrenergic receptor binding sites in membranes from both cell lines. Pretreatment with the alpha 1B-selective alkylating agent chloroethylclonidine (CEC) completely eliminated these binding sites in NB41A3 cells but caused only a 50% loss in SK-N-MC cells. Displacement with subtype-selective antagonists suggested that NB41A3 cells express only the alpha 1B subtype, whereas SK-N-MC cells express a pharmacologically heterogeneous receptor population, including both alpha 1A and alpha 1B subtypes. Norepinephrine increased [3H] inositol phosphate formation in both cell lines, but with different sensitivities to pertussis toxin and the presence of extracellular Ca2+. CEC pretreatment eliminated this response in NB41A3 cells but caused a maximal 42% reduction in SK-N-MC cells. Use of subtype-selective antagonists showed that the [3H]inositol phosphate response involved only the alpha 1B subtype in NB41A3 cells but a combination of subtypes in SK-N-MC cells. Norepinephrine induced both transient and sustained increases in intracellular Ca2+ concentrations in both cell lines, as measured with fura-2. CEC pretreatment abolished the Ca2+ response in NB41A3 cells but had little effect in SK-N-MC cells. In SK-N-MC cells the Ca2+ response was potently blocked by alpha 1A-selective antagonists. Chelation of extracellular Ca2+ eliminated the sustained component of the Ca2+ signal in both cell lines. Poly(A)+ RNA from NB41A3, DDT1MF-2, BC3H1, and MDCK-D1 cell lines showed one or more prominent transcripts (2.2-4.2 kilobases) that strongly hybridized to the hamster alpha 1B cDNA probe but not to the bovine alpha 1C or rat alpha 1D cDNA probes. Poly(A)+ RNA from SK-N-MC cells showed multiple transcripts (1.3-5.6 kilobases) that hybridized to both hamster alpha 1B and rat alpha 1D but not bovine alpha 1C cDNA probes. We conclude that NB41A3 cells contain exclusively alpha 1B-adrenergic receptors linked to inositol phosphate formation and mobilization of intracellular Ca2+, whereas at least two alpha 1-adrenergic receptor forms, which resemble the alpha 1A and alpha 1B subtypes, coexist in SK-N-MC cells. The CEC-insensitive alpha 1A-like subtype in SK-N-MC cells is capable of increasing inositol phosphate formation and mobilizing intracellular Ca2+.
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PMID:Comparison of alpha 1-adrenergic receptor subtypes and signal transduction in SK-N-MC and NB41A3 neuronal cell lines. 839 24

Neuroblastoma cells were used to examine the effect of chronic exposure to increased concentrations of glucose, galactose, or L-fucose on bradykinin-stimulated intracellular calcium release using the calcium indicator fluo-3. Bradykinin caused a concentration dependent increase in the intracellular calcium concentration and phosphoinositide hydrolysis in neuroblastoma cells. Norepinephrine, carbachol, serotonin, and thapsigargin also increased the calcium concentration. Treatment of the cells with 10(-6) M bradykinin exhausts calcium release such that the successive treatment of the cells with norepinephrine, carbachol, or serotonin results in no secondary response. In contrast, bradykinin treatment of the cells following exposure to norepinephrine, carbachol, or serotonin caused a secondary increase in calcium release. These results suggest that several hormone responsive calcium pools may exist in neuroblastoma cells or that norepinephrine, carbachol, or serotonin may not fully stimulate calcium release. Bradykinin-stimulated calcium release is not effected by chronic exposure of the cells to increased concentrations of glucose, galactose, or L-fucose. Suggesting that hormone-stimulated calcium release is not an abnormality that develops in neural cells exposed to conditions that mimic the diabetic milieu. In addition, these studies provide evidence that fluo-3 is a good fluorescent indicator for the study of calcium mobilization in cultured neuroblastoma cells.
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PMID:Effect of bradykinin on cytosolic calcium in neuroblastoma cells using the fluorescent indicator fluo-3. 849 91

Norepinephrine (NE) transporters (NETs) found in the neuronal plasma membrane mediate the removal of NE from the extracellular space, limiting the activation of adrenoceptors at noradrenergic synapses. Our previous studies with the noradrenergic neuroblastoma SK-N-SH have revealed a muscarinic receptor-triggered regulation of NET surface density and transport capacity, mediated in part by protein kinase C activation. Low abundance of NET proteins in this native cell model, however, preclude direct confirmation of altered trafficking of NET proteins. In our study, we monitored the activity and surface distribution of human NET proteins in transient and stably-transfected cell lines after application of kinase activators and inhibitors. Using hNET stably transfected HEK-293 and LLC-PK1 cells, as well as transiently transfected COS-7 cells, we demonstrate that PKC-activating phorbol esters, beta-PMA or beta-PDBu selectively diminish l-NE transport capacity (Vmax) with little change in NE Km. Effects of phorbol esters are rapid, stereospecific and blocked by protein kinase C inhibitors, staurosporine and bisindolylmaleimide I. As in SK-N-SH cells, beta-PMA induces a reduction in intact cell [3H]nisoxetine binding sites with no change in nisoxetine Kd or total membrane NET density. Cell-surface biotinylation and confocal immunofluorescence techniques confirm that protein kinase C-dependent reductions in NE transport capacity and whole-cell antagonist binding density are accompanied by reductions in cell-surface human NET protein expression. Together these findings argue for kinase-modulated protein trafficking as a potential route for acute regulation of antidepressant-sensitive NE clearance.
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PMID:Acute regulation of norepinephrine transport: II. PKC-modulated surface expression of human norepinephrine transporter proteins. 980 5

In mouse neuroblastoma x rat glioma hybrid (NG108-15) cells, we examined whether rabies virus infection affects the voltage-dependent Ca(2+) current (I(Ca)) and agonist-induced I(Ca) inhibition. The viral infection had little effect on the current-voltage relationship for peak I(Ca) or on the late I(Ca) that remained at the end of a 200-ms step depolarization. Noradrenaline and carbachol, via alpha(2)-adrenoceptors and muscarinic receptors, respectively, reduced I(Ca) concentration dependently. The maximum effect of noradrenaline was attained at 10 microM with 19.4+/-1.8% inhibition of I(Ca), which was significantly decreased to 9.9+/-1.3% after viral infection. The decrease was not reversed with 100 microM noradrenaline, suggesting that it does not result from a decrease in agonist sensitivity of cells. The maximum effect of carbachol (300 microM; 27.7+/-2.9% inhibition) remained unchanged, despite carbachol sharing intracellular signaling pathways with noradrenaline. These results indicate that in NG108-15 cells, rabies virus infection does not alter the functional expression of voltage-dependent Ca(2+) channels, but it attenuates the alpha(2)-adrenoceptor-mediated I(Ca) inhibition, possibly through some change at the receptor level.
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PMID:Rabies virus infection prevents the modulation by alpha(2)-adrenoceptors, but not muscarinic receptors, of Ca(2+) channels in NG108-15 cells. 1098 Feb 65


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