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 effects of dopamine agonists and antagonists were investigated in human neuroblastoma (HNB) tissue culture cell lines and correlated with the presence of specific membrane-bound dopamine-binding activity ("receptor"). In four HNB cell lines the dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as indicated by decreased 3H-TdR and 14C-leu incorporation in a dose-response fashion with at least 50% inhibition noted at 10(-6)M concentration of each drug. Dopamine agonists showed no significant inhibition. Scatchard analysis of competitive dopamine-binding assays in all four HNB cell lines and in five of eight solid tumors obtained at surgery demonstrated high affinity, limited-capacity binding consistent with a single class of receptor sites with receptor concentrations (Rc) ranging from 8.8 to 26.7 pmol/gm wet weight of tissue with dissociation constants (KD) from 0.40 to 6.6 nmol/L, compared with a mean Rc of 28.1 +/- 5.2 pmol/gm wet weight of tissue and KD = 0.38 +/- 0.09 nmol/L in receptor-rich dog caudate nucleus, the normal dopamine-sensitive control. Survival was prolonged after inoculation of the SK-N-AS cell line into nude mice and subsequent domperidone administration by 50% (24 days after drug initiation versus 16 days in control mice). These data demonstrate inhibition of macromolecular synthesis in HNB by dopamine antagonists and suggest that dopamine receptor is associated with this inhibition. The determination of dopamine receptors may prove useful in the selection of dopamine antagonists as specific chemotherapy for patients with neuroblastoma.
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PMID:Inhibition of human neuroblastoma by dopamine antagonists. 402 14

The presence of biogenic amines in cultured cells of mouse neuroblastoma C-1300 (clone NB-2a) was suggested by fluorescence-microscope histochemistry. Incubation in media containing L-[(14)C]tyrosine and L-[(14)C]tryptophan for 24 h, followed by high-voltage electrophoresis, radiochromatogram scanning, and scintillation counting, confirmed the presence of [(14)C]dopamine, [(14)C]norepinephrine, [(14)C]epinephrine, [(14)C]serotonin, [(14)C]tyramine, and [(14)C]octopamine. Dopamine, norepinephrine, epinephrine, and serotonin were demonstrated spectrophotofluorometrically in concentrations, expressed as micrograms amine per milligram protein, of 1.19, 0.027, 0.038, and 0.148, respectively, for cells in a stationary growth phase. Fluorescence-microscope histochemistry also suggested the presence of biogenic amines in cultured astrocytoma cells (cell line C6). Spectrophotofluorometric assay of cells in a stationary growth phase demonstrated intracellular dopamine, norepinephrine, epinephrine, and serotonin in concentrations significantly lower than those of neuroblastoma cells.
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PMID:Biogenic amines in cultured neuroblastoma and astrocytoma cells. 437 Sep 24

Dopamine-beta-hydroxylase activity is present in mouse neuroblastoma C-1300 tumors. The activity is proportional to the weight of the tumor. Serum activity is markedly increased in mice that bear the tumors. Treatment of mice with 5-bromodeoxyuridine causes marked inhibition of tumor growth and decrease of dopamine-beta-hydroxylase activity in the serum. The histochemical studies reveal that 1-5% of the cells in mouse C-1300 neuroblastoma tumors contain catecholamines and that catecholamine-containing processes terminate mainly around blood vessels of the tumor. Dopamine-beta-hydroxylase is present in clonal neuroblastoma cell lines. The cell line with the greater tendency to form axon-like processes has a higher activity of this enzyme.
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PMID:Dopamine- -hydroxylase activity in mouse neuroblastoma tumors and in cell cultures. 450 66

The DOPA-content in neuroblastoma clone N1E-115 is higher than the dopamine or noradrenaline content. Blockade of tyrosine hydroxylase by alpha-methyl-p-tyrosine (1 X 10(-3) M) resulted in a decrease of cellular DOPA-content to 24.9% after 4 hr. The accumulation of DOPA in these cells which is probably due to limited activity of l-aromatic amino acid decarboxylase led us to use DOPA-content as a measure of tyrosine hydroxylase (TH) activity. Dopamine and especially apomorphine were effective at low concentrations (dopamine IC50 1 X 10(-5) M, apomorphine 2 X 10(-7) M); lisuride had no effect on TH-activity. The low effective dose of apomorphine and the failure of lisuride to influence TH-activity are comparable to the observations in striatal synaptosomal preparations and make the N1E-115 clone a suitable model for studying the mechanism of TH-regulation. However, since haloperidol (1 X 10(-5) M) did not reverse the apomorphine-induced blockade of TH, a receptor-mediated blockade of TH seems to be improbable.
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PMID:Mouse neuroblastoma clone N1E-115: a suitable model for studying the action of dopamine agonists of tyrosine hydroxylase activity. 612 55

Dopamine and dopamine receptor agonists were found to inhibit adenylate cyclase activity dose-dependently in a neuroblastoma X Chinese hamster brain explant hybrid cell line NCB-20. Apomorphine (with an IC50 value of 10 nM) was the most effective inhibitor, followed by 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthaline (ADTN), dopamine, and N-dipropyldopamine. The inhibition was potently reversed by sulpiride, butaclamol, and flupenthixol in a stereospecific manner, but was unaffected by yohimbine, except at high concentrations. Clonidine also inhibited adenylate cyclase activity in these cells and this was reversed by the alpha 2-adrenoreceptor antagonist yohimbine, but not by sulpiride. [D-Ala2, D-Leu5] Enkephalin inhibited adenylate cyclase activity in NCB-20 cells at nanomolar concentrations; this was reversed by naloxone. All three inhibitory neurotransmitters were able to reverse the stimulation of cyclic AMP synthesis by serotonin or prostaglandin E1. The dopamine receptor that modulates cyclic AMP synthesis in NCB-20 cells is pharmacologically quite distinct from a high-affinity spiperone binding site identified in these cells, but shows the pharmacologic specificity of the "D2" receptor previously described in mammalian brain.
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PMID:Specific receptor-mediated inhibition of cyclic AMP synthesis by dopamine in a neuroblastoma X brain hybrid cell line NCB-20. 633 Feb 99

C-1300 murine neuroblastoma ( MNB ) contains the catecholamine biosynthetic pathway. This study investigated manipulation of this pathway for effects on cell growth and survival in tumor-bearing mice, and to correlate these findings with specific membrane-bound dopamine-binding activity. The dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as demonstrated by decreased [3H]TdR and [14C]leu incorporation in a dose-response fashion; 56, 49, and 43% inhibition was noted at 10(-6) M concentration of each drug, respectively, with no loss of cell viability. Dopamine agonists showed no significant inhibition. Scatchard analysis of dopamine binding was consistent with a single class of receptor sites with a mean concentration of 13.2 +/- 2.0 pmole/g wet weight of tissue and mean dissociation constant (Kd) = 0.69 +/- 0.38 nM, compared to a mean receptor concentration of 28.1 +/- 5.2 pmole/g wet weight of tissue and Kd = 0.38 +/- 0.09 nM in receptor-rich dog caudate nucleus, the normal control. A/J mice injected with 1 X 10(6) tumor cells and treated with daily pimozide or domperidone had a significant increase in disease-free survival when compared to controls (15 versus 8.5 days, P less than 0.001) as well as a significant increase in overall survival (35 versus 25 days, P less than 0.001). These data suggest that dopamine antagonists inhibit macromolecular synthesis in the C-1300 MNB . The inhibition of MNB tumor growth in vivo by dopamine antagonists suggests a specific chemotherapeutic approach to neuroblastoma, possibly mediated by dopamine receptors.
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PMID:Inhibition of murine neuroblastoma growth by dopamine antagonists. 672 21

Dopamine-beta-hydroxylase (D beta H), a glycoprotein enzyme which converts dopamine into noradrenaline, was purified from C1300 mouse neuroblastoma and used to raise antibodies in rabbits. Using an indirect immunofluorescence technique the cellular localization of D beta H in C1300 mouse neuroblastoma was compared with that of the superior cervical ganglion. C1300 neuroblastoma D beta H was found to be predominantly localized in the plasma membrane, in contrast to its intracellular localization in the superior cervical ganglion of A/J mice. At least part of the enzyme was found to be associated with the external side of the plasma membrane.
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PMID:Immunohistochemical evidence for a plasma membrane localization of dopamine-beta-hydroxylase in the mouse neuroblastoma. 699 45

Uptake of catechol isoquinolines to dopamine cells was studied using human dopaminergic neuroblastoma SH-SY5Y cells. Only (R)-1,2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-1,2-DiMeDHTIQ] was transported by dopamine uptake system, while (S)-1,2-DiMeDHTIQ, (R)- and (S)-1-methyl-6,7-dihydroxy-tetrahydroisoquinoline, and 1,2-dimethyl-6,7-dihydroxyisoquinolinum ion were not. Kinetical study showed that the uptake of (R)-1,2-DiMeDHTIQ followed the Michaelis-Menten equation, and the values of the Michaelis constant and the maximal velocity were obtained to be 102.6 +/- 36.9 microM and 66.0 +/- 2.8 pmol/min/mg protein. Dopamine was found to inhibit (R)-1,2-DiMeDHTIQ uptake competitively. These results suggest that the selective uptake by dopamine transporter may account for the specific neurotoxicity of (R)-1,2-DiMeDHTIQ to dopamine neurons.
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PMID:Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine transport system. 773 8

1. Tyrosine and tryptophan, as well as 26 metabolites of these amino acids, were analyzed simultaneously in urine specimens from patients with neuroblastoma and control infants by a three-dimensional HPLC system to develop an early diagnosis. 2. Levels of detected compounds in urine from patients with neuroblastoma were generally higher in the case of catecholamines and lower in the case of indolalkylamines than those in controls. 3. The pathways of Dopamine-3,4-Dihydroxyphenylacetic acid-Vanillylmandelic acid, Dopamine-3-Methoxy-4-hydroxyphenylethylene glycol-Vanillylmandelic acid and Tyrosine-4-Hydroxyphenylacetic acid-4 were, in particular, found to be active in patients with neuroblastoma.
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PMID:Simultaneous analyses of monoamines and their metabolites in urine specimens of patients with neuroblastoma. 790 Sep 60

Transfection of a human dopamine D3 receptor cDNA in a neuroblastoma-glioma hybrid cell line (NG 108-15) provided clonal cell lines stably expressing up to 600 fmol per mg protein of [125I]iodosulpiride binding sites. Dopamine and several agonists distinguished two receptor-affinity states in membranes. In the case of dopamine, the high-affinity state (Ki = 0.9 nM, 30% of total binding) was completely converted into a low-affinity state (Ki = 57 nM) in the presence of 10 microM guanosine-5'-O-(3-thiotriphosphate). In addition to these two sites, a site with a very low affinity for dopamine was evidenced in whole cells. The dopamine D3 receptor mediated two responses: c-fos activation, as measured by the appearance of Fos-like immunoreactivity, and increased mitogenesis, as measured by incorporation of [3H]thymidine. The Fos-like immunoreactivity appeared within 30 min, lasted 2 h and was blocked by the partially selective dopamine D3 receptor compound (+)-UH 232 (cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin). The mitogenic effect, which occurred after a lag time (over 2 h stimulation), was produced with subnanomolar potency and full intrinsic activity by several compounds previously identified as dopamine D2 receptor agonists, e.g. quinpirole, (+)-7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and RU 24926 (N-n-propyl-di-beta(3-hydroxyphenyl)-ethylamine), and was reversibly blocked by (+)-UH 232 (Ki = 9 nM). Talipexole (B-HT 920, 5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin) was identified as a partial agonist at the dopamine D3 receptor. Dopamine D3 receptor-mediated mitogenesis was potentiated by a phorbol ester and was abolished by pretreatment with pertussis toxin. A mitogenic effect of same amplitude was elicited by bradykinin or carbachol, both acting through constitutive receptors. Bradykinin markedly activated inositol phosphate turnover, and had no effect on forskolin-stimulated cyclic AMP accumulation. Carbachol inhibited forskolin-stimulated cyclic AMP accumulation and had no effect on inositol-phosphate turnover. Quinpirole had no effect on any of these second messenger pathways. Thus, in transfected NG 108-15 cells, the dopamine D3 receptor is coupled to a pertussis toxin-sensitive G protein and mediates two possibly unrelated biological effects, through initial biochemical events that remain to be identified.
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PMID:Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line. 795 35


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