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 clonal human neuroblastoma cell line SK-N-SH-SY5Y was previously shown to express mu-opioid and alpha 2-adrenoceptors which are both negatively coupled to adenylyl cyclase. Because of the potential use of alpha 2-agonists in the treatment of narcotic dependence, we tested the interactions among he alpha 2-agonists, clonidine and norepinephrine, and morphine on AC in SH-SY5Y cells. Pretreatment with retinoic acid resulting in partial neuronal differentiation greatly enhanced the cells' sensitivity towards adenylyl cyclase stimulation by prostaglandin E1, and its inhibition by morphine and alpha 2-agonists. Norepinephrine (EC50 = 69 nM) maximally inhibited prostaglandin E1-stimulated cAMP accumulation (by approximately 83%), and the alpha 2-agonist yohimbine reversed these effects. Clonidine (EC50 = 32 nM) was a partial agonist, with 50 to 60% maximal inhibition. The combined effects of morphine (maximum approximately 70% inhibition) and norepinephrine exceeded the effect of either agent alone, yielding more than 90% inhibition of prostaglandin E1-stimulated cAMP accumulation. As previously reported for morphine, only a partial tolerance was observed for adenylyl cyclase inhibition by norepinephrine. Further, no cross-tolerance was observed between clonidine and morphine. The combined results indicate that mu-opioid receptors and an alpha 2-adrenoceptor subtype are colocalized on the same cells in SH-SY5Y culture, which hence serves as a model to study opioid-alpha 2-adrenergic interactions.
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PMID:Interaction among mu-opioid receptors and alpha 2-adrenoceptors on SH-SY5Y human neuroblastoma cells. 135 61

Clonidine-displacing substance (CDS) isolated from bovine brain potently inhibits clonidine binding and elicits contraction of gastric smooth muscle. We sought to determine if CDS was contained in neuron-like clonal cells (neuroblastoma X glioma hybrid NG108-15). Extracts were prepared from osmotically shocked P2 fractions of NG108-15 cells. One unit of CDS, as defined by a [3H]p-aminoclonidine radioreceptor assay using bovine frontal cortex membranes, was obtained from each 1.3 million cells processed. CDS isolated from NG108-15 cells was biologically active on gastric smooth muscle. NG108-15 cells may serve as a model system for the study of this endogenous clonidine-like ligand.
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PMID:Neuroblastoma-glioma hybrid cells contain clonidine-displacing substance. 261 78

Clonidine and several analogues of clonidine are shown to be useful probes for alpha 2-adrenergic receptors in a comparative study of ligand binding and inhibition of adenylate cyclase. The alpha-adrenergic properties of a new potential probe, N-(4-hydroxyphenacetyl)-4-aminoclonidine hydrochloride, are described. [3H]Clonidine binds to alpha-receptors of NG108-15 neuroblastoma X glioma hybrid cell membranes with Kd values of 1.7 and 33 nM for putative high-affinity and low-affinity sites, respectively. p-Aminoclonidine and hydroxyphenacetyl aminoclonidine displace [3H]clonidine from the high-affinity sites with Kd values of 2.3 and 5.8 nM, respectively. Rat brain alpha 2-receptors also exhibit high affinity toward clonidine, p-aminoclonidine, and hydroxyphenacetyl aminoclonidine, as determined by displacement of specifically bound [3H]clonidine. Clonidine, p-amino-clonidine, and hydroxyphenacetyl aminoclonidine elicit modest inhibition (up to 24%) of NG108-125 adenylate cyclase by interaction with alpha 2-receptors (Kd,app 300, 30, and 130 nM, respectively); these compounds also partially reverse the inhibition elicited by (--)-norepinephrine. Components of the adenylate cyclase assay mixture, particularly ATP, GTP, sodium ions, and a nucleoside-triphosphate-regenerating system, decrease the high-affinity [3H]clonidine binding to NG108-15 membranes; in the presence of these components, alpha-receptors possess only low affinity (Kd 43 nM) for [3H]clonidine. The results are consistent with the concept that certain components required for the receptor-mediated inhibition of adenylate cyclase convert alpha 2-receptors from a high-affinity inactive state to a low-affinity active state.
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PMID:Interaction of clonidine and clonidine analogues with alpha-adrenergic receptors of neuroblastoma X glioma hybrid cells and rat brain: comparison of ligand binding with inhibition of adenylate cyclase. 626 Apr 85

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

The effects of adrenergic receptor ligands on uptake and storage of the radiopharmaceutical [125I]metaiodobenzylguanidine (MIBG) were studied in the human neuroblastoma cell line SK-N-SH. For uptake studies, cells were incubated for 15 min with varying concentrations of alpha-agonist (clonidine, methoxamine, and xylazine), alpha-antagonist (phentolamine, tolazoline, phenoxybenzamine, yohimbine, and prazosin), beta-antagonist (propranolol, atenolol), beta-agonist (isoprenaline and salbutamol), mixed alpha/beta antagonist (labetalol), or the neuronal blocking agent guanethidine, prior to the addition of [125I]MIBG (0.1 microM). The incubation was continued for 2 h and specific cell-associated radioactivity was measured. For the storage studies, cells were incubated with [125I]MIBG for 2 h, followed by replacement with fresh medium with or without drug (MIBG, clonidine, or yohimbine). Cell-associated radioactivity was measured at various times over the next 20 h. Propanolol reduced [125I]MIBG uptake by approximately 30% (P<0.01) at all concentrations tested, most likely due to nonspecific membrane changes. However, incubation with the other beta-agonists or antagonists failed to elicit significant reductions in uptake. In contrast, all of the alpha-agonists significantly inhibited uptake (P<0.05); guanethidine >xylazine >clonidine=methoxamine. The alpha-antagonists demonstrated a broad range of inhibition (phenoxybenzamine >>phentolamine >prazosin >>yohimbine=tolazoline)(P< 0.05). The mixed ligand, labetolol, inhibited MIBG uptake in a dose-dependent manner with an apparent IC50 of 0.65 microM. The retention studies demonstrated that unlabeled MIBG caused profound self-inhibition (P<0.01). Clonidine produced a modest inhibition of retention and yohimbine had no effect. Labetalol, phenoxybenzamine, guanethidine, and propranolol reduced uptake of [125I]MIBG by neuroblastoma cells in culture. Although only labetalol has been reported to cause false-negative MIBG scans, our results suggest that these other drugs have the potential to interfere with MIBG imaging and therapy, particularly at high doses. Adrenergic drugs did not alter cytoplasmic retention of [125I]MIBG in neuroblastoma cells but may have potential in tumors such as phenochromocytoma, where granular storage of MIBG has been observed. Inhibition of [125I]MIBG retention by unlabeled MIBG supports the use of high specific activity radioiodinated MIBG for both diagnosis and therapy.
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PMID:Effect of adrenergic receptor ligands on metaiodobenzylguanidine uptake and storage in neuroblastoma cells. 914 35

The alpha2-adrenoceptor mediating inhibition of forskolin-stimulated cyclic AMP accumulation in human neuroblastoma SH-SY5Y cells was further characterized. The alpha2-adrenoceptor agonists, UK 14,304 (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline), oxymetazoline, guanfacine, (-)-noradrenaline and clonidine concentration-dependently decreased cyclic AMP accumulation in this cell line (Emax ca. 50% inhibition). Agonist pEC50 values ranged between 6.7 and 7.8. Clonidine was a partial agonist. The effects of UK 14,304 were blocked after a pertussis toxin treatment. The concentration-response curves of UK 14,304 were shifted to the right in a parallel manner by the following antagonists (mean pK(B) values): yohimbine (8.17), idazoxan (7.63), prazosin (6.66), 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2 H,4H) isoquinolindione (ARC 239; 7.12) and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB-4101; 8.12). The relatively high pKB values of prazosin and ARC 239 point to a non-alpha2A-adrenoceptor-mediated effect. The relatively high pK(B) value of WB-4101 further characterizes the alpha2-adrenoceptor in SH-SY5Y cells as being of the alpha2C subtype. The analysis of the expression of alpha2-adrenoceptor subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the exclusive presence of alpha2C-adrenoceptor mRNA in SH-SY5Y cells. We propose that inhibition of forskolin-stimulated cAMP accumulation in SH-SY5Y cells be used as a functional model of human, native alpha2C-adrenoceptors.
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PMID:Functional alpha2C-adrenoceptors in human neuroblastoma SH-SY5Y cells. 1037 21

Excess secretion of any of the adrenal cortical or medullary hormones contributes to a number of well-known clinical syndromes.. They may result from benign or malignant adrenal tumours, adrenal hyperplasia or, least frequently, from extra-adrenal disease. Differentiation among these possibilities is often impossible on clinical or biochemical grounds alone. Location of the site(s) of excess hormone production in the past depended on relatively insensitive or invasive radiological methods. The non-invasive evaluation began with X-ray computed tomography but the functional significance of anatomical abnormalities cannot be determined from CT scan. Incorporation of specific radiopharmaceuticals into the abnormal tissues allows scintigraphic localization of functional abnormalities with a high degree of efficacy. The combination of adrenal scintigraphy and kompjuterizovanom tomografijom CT or magnetskom rezonancijom MRI should in most cases obviatc the need for more invasive procedures. Phaeochromocytoma is rare in hypertensive population, affecting only an estimated of 0.1%. However, a high index of suspicion is essential, since these tumours have potentially life-threatening cardiovascular effects and their successful resection is curative. Important clinical clues include the presence of orthostatic hypotension in an untreated hypertensive, resistance of hypertension to standard therapy (including possible exacerbation by (beta-blockers). In most cases, the diagnosis can be established by demonstrating high levels of free catecholamines and their metabolites (metanephrines and Vanillylmandelic acid). Clonidine test may be important in some cases. The purpose of this study is to point that metaiodobenzylguanidine (mlBG) has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma. The first successful schinigraphic demonstration of phaeochromocytomas in man was reported in 1981, using a new radiopharmaceutical, 131l-metaiodobenzylguanidinc (mlBG). mlBG is an aralkyl-guanidine which structurally resembles noradrenaline sufficiently to be recognized and be stored in the catecholamine storage vesicles. Whereas unstored noradrenaline is rapidly degraded, the halogenated benzyl ring of mlBG conlers resistance to catechol-o-methyltransferase (COMT) while its guanidino side-chain is resistant to monoamine oxidase (MAO). Uptake of mIBG is inhibited by some inhibitors (reserpine, tricyclic antidepressants, cocaine, labetalol, calcium-chanel blockers...). 131I-mlBG is normally taken up by liver, spleen, myocardium and salivary glands. Thyroid uptake ol liberated radioiodide will also occur unless the thyroid is blocked with stable iodide. The normal adrenal glands are usually not seen but faint uptake may be visible 48-72 h after injection in up to 16% of cases. Hepatic uptake is maximal at 24 h, declining to very low levels by 72 h (even more rapid in patients with phaeochromocytoma. Dosimetric corlsiderations limit the amount of 131l-mlBG that is administered for diagnostic studies. This, coupled with the low detection efficiency of gamma cameras for the 364 keV photon of 131l, led to the introduction of 131l-mlBG as an adrenomedullary scintigraphic agent of choice. In our department we started with mIBG scintigraphy in 1985 and we treated near 1000 patients. In this study we are talking about 180 patients from the beginning of 1996 to the end of 2001 all treated with 131l-mlBG. Like the other worldwide experience with this agent our sensitivity was 88.58% and specificity of 98.46%. Positive predictive value was 88.5% and negative predictive value was 93.46%. False negative results were 6.52% and there were no false positive results. After all we can say that mlBG has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma and neuroblastoma. Other radiolabelled aralkylamines have been examined as potential adrenal medullary scintigraphic agents. None has demonstrated superiority over mlBG in animal or limited human studies. 131l-mlBG should always be considered the radiopharmaceutical of choice for imaging purposes if it is available. 131l-mlBG in high doses is successfully used in therapy of malignant phaeochromocytoma and especially in nuroblastoma.
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PMID:[Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine]. 1258 93