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)

We describe characteristics of a selective endothelin (ET) ET(B) receptor antagonist, BQ-788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine], which is widely used to demonstrate the role of endogenous or exogenous ETs in vitro and in vivo. In vitro, BQ-788 potently and competitively inhibited (125)I-labeled ET-1 binding to ET(B) receptors in human Girrardi heart cells (hGH) with an IC(50) of 1.2 nM, but only poorly inhibited the binding to ET A receptors in human neuroblastoma cell line SK-N-MC cells (IC(50), 1300 nM). In isolated rabbit pulmonary arteries, BQ-788 showed no agonistic activity up to 10 microM and competitively inhibited the vasoconstriction induced by an ET(B)-selective agonist (pA(2), 8.4). BQ-788 also inhibited several bioactivities of ET-1, such as bronchoconstriction, cell proliferation, and clearance of perfused ET-1. Thus, it is confirmed that BQ-788 is a potent, selective ET(B) receptor antagonist. In vivo, in conscious rats, BQ-788, 3 mg/kg/h, i.v., completely inhibited a pharmacological dose of ET-1- or sarafotoxin6c (S6c) (0.5 nmol/kg, i.v.)-induced ET(B) receptor-mediated depressor, but not pressor responses. Furthermore, BQ-788 markedly increased the plasma concentration of ET-1, which is considered an index of potential ET(B) receptor blockade in vivo. In Dahl salt-sensitive hypertensive (DS) rats, BQ-788, 3 mg/kg/h, i.v., increased blood pressure by about 20 mm Hg. It is reported that BQ-788 also inhibited ET-1-induced bronchoconstriction, tumor growth and lipopolysaccharide-induced organ failure. These data suggest that BQ-788 is a good tool for demonstrating the role of ET-1 and ET(B) receptor subtypes in physiological and/or pathophysiological conditions.
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PMID:BQ-788, a selective endothelin ET(B) receptor antagonist. 1207 May 34

Tumours of the Ewing's sarcoma (ES) family and neuroblastoma (NBL) were examined by reverse transcriptase-PCR for expression of mRNA for endothelin (ET) receptors ET-A and ET-B, and the ligands ET-1, ET-2 and ET-3. The effect of ET-1, ET-3, an ET-1-neutralizing antibody and ET-A receptor antagonist BQ-123 on cell proliferation was examined using an ELISA. Loss of ET-B receptor mRNA occurred in 57% of ES and 42% of NBL tumours. This appeared to be associated with the presence of metastatic disease and disease progression. ET-A receptor mRNA was expressed in all ES and 85% of NBL tumours, and in all ES and NBL cell lines examined. All ET ligands were detected in NBL cell lines, but only ET-1 and ET-2 were expressed in ES cell lines. Treatment of ES and NBL cells with ET-1 increased proliferation, but ET-3 had no effect. Incubation of ES and NBL cells with an ET-1-neutralizing antibody or BQ-123 decreased proliferation. The ET-3 ligand and ET-B receptor may be associated with migration and metastasis of ES and NBL, whereas ET-1 (acting through the ET-A receptor) may regulate their proliferation.
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PMID:Endothelins may modulate invasion and proliferation of Ewing's sarcoma and neuroblastoma. 1219 14

A bioassay-guided fractionation of the 80 % ethanolic extract from Bocconia frutescens L. roots, showing a dose-dependent inhibitory effect towards both [(3)H]-angiotensin II and [(3)H]-BQ-123 binding to the human angiotensin II AT 1 and endothelin 1 ET(A) receptors, led to an alkaloidal subfraction as the only responsible fraction for the activity of the whole extract. Among the alkaloids present in this fraction sanguinarine and chelerythrine were significant inhibitors of [(3)H]-angiotensin II binding (hAT 1 receptor), with IC(50) values within the micromolar range. On the contrary, the [(3)H]-BQ-123 binding (ET(A) receptor) was only weakly inhibited. Moreover, other members of the isoquinoline alkaloid family such as chelidonine and some protoberberine alkaloids exhibited no affinity for the two receptors. The present work shows the possible structure-activity relationship for these benzophenanthridine alkaloids on a screening bioassay using both stably transfected Chinese hamster ovary (CHO) and the human neuroblastoma SK-N-MC cells. Furthermore, the ability of these compounds to block AT(1) and/or ET(A) receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension.
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PMID:Inhibitory activity on binding of specific ligands to the human angiotensin II AT(1) and endothelin 1 ET(A) receptors: bioactive benzo[c]phenanthridine alkaloids from the root of Bocconia frutescens. 1235 84

Endothelins (ETs), which were originally found to be potent vasoactive transmitters, were known to be implicated in nervous system, but the mode of mechanism remains unclear. ETs (ET-1, ET-2, and ET-3) were added to HN33 (mouse hippocampal neuron chi neuroblastoma) cells. Among the three types of ET, only ET-1 increased the intracellular calcium levels in a PLC dependent manner with the induction of ERK 1/2 activation. As the result of ET-1 exposure, the survival rate of HN33 cells and the PKCalpha translocation into the plasma membrane were increased. We suggest that ET-1 participated in the neuroprotective effect involving the calcium-PKCalpha-ERK1/2 pathway.
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PMID:Endothelin 1 protects HN33 cells from serum deprivation-induced neuronal apoptosis through Ca(2+)-PKCalpha-ERK pathway. 1830 2


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