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

3H-5-HT (serotonin) binding and its displacement by various specific subtype ligands and effects on the phosphoinositides (PI) turnover were studied in cultured C6 glioma and N2 neuroblastoma cells from rodents. Saturation analysis of 3H-5-HT binding to C6 cells revealed that its Kd and Bmax were 3.0 nM and 18.0 pmole/mg protein respectively. DOI.HCl (5-HT2 agonist) and ketanserin (5-HT2 antagonist) had the highest affinities in the drug-displacement of 3H-5-HT binding to C6 cells studied. The IC50 values for DOI-HCl and ketanserin were 7.5 x 10(-7) and 3.5 x 10(-8) M respectively. 5-HT also induced 3H-PI breakdown and generated 3H-IP. The EC50 values for 5-HT for this event were in the dose range between 0.5 to 1.5 microM, and this 5-HT-induced response could be blocked by 5-HT2 antagonist ketanserin more effectively than the 5-HT1 antagonist or 5-HT3 antagonist studied. 3H-5-HT binding to N2 cells revealed that its Kd and Bmax were 4.0 nM and 80 pmole/mg protein respectively in the saturation analysis study. The drug-displacement of this binding revealed that MDL 72222 (5-HT3 antagonist) had a higher affinity than ketanserin. The IC50 values for MDL 72222 and ketanserin were 10 nM and 10 microM respectively, when 3 nM of 3H-5-HT was used. Our results indicate that the predominant receptor subtype of 5-HT in C6 and N2 cells are 5-HT2, and 5-HT3 respectively, and that the PI turnover is linked to 5-HT2, but not 5-HT3 receptor activation.
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PMID:Characterization of 3H-serotonin (5-HT) binding and effects on the phosphoinositides (PI) turnover in cultured C6 glioma and N2 neuroblastoma cells from rodents. 133 7

5-Hydroxytryptamine3 (5-HT3) receptors from N1E-115 neuroblastoma cells were solubilized using 1.1% n-octylglucoside; five other detergents were less effective. Purification was achieved by affinity chromatography using immobilized GR119566X and biospecific elution with quipazine. Saturation analyses with [3H] GR67330 binding revealed high affinity binding to homogeneous populations of sites in both the solubilized (Kd = 0.05 +/- 0.02 nM) and purified (Kd = 0.10 +/- 0.04 nM) preparations. Competition experiments indicated that the solubilized and purified receptor preparations retained the characteristics observed in N1E-115 cells in vivo. Polyacrylamide gel electrophoresis of the purified receptor revealed a single protein band of 54.7 +/- 1.3 kDa. The purified receptor was incorporated into liposomes, and the functional integrity of the protein was demonstrated by measurement of m-chlorophenylbiguanide-stimulated 22Na uptake. Saturation analysis of the reconstituted preparation revealed a Kd of 0.24 +/- 0.07 nM and suggested that 0.2% of 5-HT3 receptors present in the original membrane preparation had been incorporated into liposomes.
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PMID:Solubilization, purification, and functional reconstitution of 5-hydroxytryptamine3 receptors from N1E-115 neuroblastoma cells. 137 Jul 6

The action of a novel 5-HT3 receptor antagonist, AS-5370, has been studied on two electrophysiological models for 5-HT3 receptors: whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma (NG108-15) cells and grease-gap recordings from rat isolated vagus nerve. The 5-hydroxytryptamine (5-HT)-induced fast inward current of voltage-clamped NG108-15 cells was antagonized by 1 nM AS-5370 in an insurmountable manner. On the rat vagus, AS-5370 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner. The IC50 for AS-5370 on the rat vagus was 0.3-1.0 nM. The EC50 for 5-HT on the rat vagus was not appreciably affected by AS-5370. On the rat vagus, the (R) enantiomer of AS-5370 was about 30 times more potent than the (S) enantiomer. The antagonist action of AS-5370 on these two cell types was compared with that of (+)-tubocurarine. Unlike tubocurarine, the effect of AS-5370 on NG108-15 cells was not readily reversed during wash. On the rat vagus, tubocurarine antagonized in a competitive manner with an IC50 of 0.3-1.0 microM (pKb = 7.2). It is concluded that AS-5370 is a potent 5-HT3 receptor antagonist on both NG108-15 cells and the rat vagus, but it does not act in a competitive manner.
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PMID:AS-5370 potently antagonizes 5-HT3 receptor-mediated responses on NG108-15 cells and on the rat vagus. 139 40

In radioligand binding experiments, MDL 73147EF and MDL 74156 inhibited the binding of [3H]GR65630 to 5-hydroxy-tryptamine3 (5-HT3) binding sites on membranes prepared from NG108-15 neuroblastoma x glioma cells. The calculated dissociation constants (KI) were 20.03 +/- 6.58 and 0.44 +/- 0.18 nM, respectively (means +/- S.E.M., n = 6 and 9, respectively). Application of 5-HT (10-50 microM) to voltage-clamped NG108-15 cells elicited a rapidly desensitizing inward membrane current, characteristic for the activation of 5-HT3 receptors. The 5-HT-induced membrane current was suppressed in a reversible, concentration-dependent manner by MDL 73147EF and MDL 74156EF. The concentrations required to block half the 5-HT response (IC50) were 3.8 and 0.1 nM, respectively. It is concluded that both compounds are potent and reversible antagonists at 5-HT3 receptors in this neuroblastoma cell line.
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PMID:Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesilate) and MDL 74156 in NG108-15 neuroblastoma x glioma cells. 139 53

The effect of the novel agonist, 1-(m-chlorophenyl)-biguanide (mCPBG) was examined on 5-HT3 receptors in NG108-15 mouse neuroblastoma x rat glioma hybrid cells, using whole-cell voltage-clamp and radioligand binding on intact cells. Electrophysiological studies showed that mCPBG is a partial agonist, with an EC50 of 3.1 microM. Displacement of the selective 5-HT3 receptor antagonist [3H]GR65630 by mCPBG revealed a Ki of 14.2 nM. The study suggests that mCPBG may have a high affinity for desensitized 5-HT3 receptors and also revealed some differences between 5-HT3 receptors in NG108-15 and N1E-115 cells.
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PMID:5-HT3 receptors in NG108-15 neuroblastoma x glioma cells: effect of the novel agonist 1-(m-chlorophenyl)-biguanide. 140 96

The 5-hydroxytryptamine (5-HT)3 receptor blocking properties of YM060, [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride], were examined by electrophysiological and radioligand binding studies. Results were compared with those for ondansetron, granisetron and the enantiomer (S-form) of YM060. 5-HT and 2-methyl-5-HT, a selective 5-HT3 receptor agonist, induced dose-dependent depolarizations of rabbit nodose ganglion with ED50 values of 24.0 (19.9-29.1) and 40.1 (30.9-52.1) nmol, respectively (geometric mean, 95% CL). YM060, ondansetron, granisetron and the S-form dose-dependently inhibited 5-HT-induced depolarizations with IC50 values of 3.85 (2.47-5.98), 1.55 (1.26-1.91), 1.45 (1.18-1.79) and 13.5 (11.2-16.2) nM, respectively. Methysergide, a 5-HT1-like and 5-HT2 receptor antagonist, at a concentration of 10(-5) M had no effect on responses to 5-HT. YM060 up to 10(-5) M produced no significant depression of depolarizing responses to 1,1-dimethyl-4-phenylpiperazinium iodide and gamma-aminobutyric acid. YM060, ondansetron, granisetron and the S-form displaced specific binding of [3H]GR65630 to N1E-115 neuroblastoma cell membranes with Ki values of 0.091 (0.086-0.097), 7.03 (5.96-8.01), 2.02 (1.74-2.30) and 10.3 (9.96-10.6) nM, respectively. These results show that YM060, compared with ondansetron and granisetron, has considerably higher affinity for 5-HT3 receptors in N1E-115 cells and slightly less potent 5-HT3 receptor antagonistic activity in rabbit nodose ganglion. Moreover, the isomeric activity ratio (R-form/S-form) was approximately 112 in N1E-115 cells and no greater than 4 in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of YM060, a potent and selective 5-hydroxytryptamine3 receptor antagonist, in rabbit nodose ganglion and N1E-115 neuroblastoma cells. 146 24

The effects of inorganic lead (Pb2+) on the ion currents mediated by (1) neuronal nicotinic acetylcholine (ACh) receptors, (2) serotonin 5-HT3 receptors, as well as (3) voltage-dependent Ca2+ and Na+ channels have been investigated in voltage clamped mouse neuroblastoma cells. The nicotinic ACh receptor-ion channel complex appeared more sensitive to Pb2+ than the other ion channels investigated. Low concentrations of Pb2+ (1 nM - 3 microM) reduced the peak amplitude of the ACh-induced inward current to 74%-10% of the control value in a concentration-dependent manner. However, between 10 microM and 100 microM Pb2+ the blocking effect was reversed, while the decay of the ACh-induced inward current was delayed. These effects of Pb2+ on the nicotinic receptor-mediated inward current can be described by the sum of two sigmoidal concentration-effect curves with an IC50 value of 19 nM and an EC50 of 21 microM and with slope factors of -0.5 and 0.8, respectively. The current mediated by 5-HT3 receptors was less potently blocked by Pb2+ (IC50 = 49 microM; slope factor = -0.3). In addition, Pb2+ blocked the ion current through voltage-dependent Ca2+ channels. The IC50 value of the concentration-effect curve of block of transient type Ca2+ channels by Pb2+ is 4.8 microM and the slope factor is -0.9. Voltage-dependent Na+ channels were not affected by Pb2+ up to 100 microM. At concentrations greater than 1 microM, Pb2+ also induced a noninactivating inward current. The present results show that modification of neuronal nicotinic receptor function may contribute to neurotoxic effects of Pb2+ poisoning.
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PMID:Nanomolar concentrations of lead selectively block neuronal nicotinic acetylcholine responses in mouse neuroblastoma cells. 169 Apr 61

The effect of acute ethanol (EtOH) exposure on 5-HT3 receptor-mediated ion current was examined in whole-cell patch-clamp recordings from NCB-20 neuroblastoma cells. The physiologic and pharmacologic properties of 5-HT-activated ion current in NCB-20 cells indicated that it was mediated by 5-HT3 receptors. EtOH potentiated 5-HT3 receptor-mediated current in a concentration-dependent manner at concentrations (25-100 mM) which are achieved during EtOH intoxication in vivo.
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PMID:Ethanol potentiation of 5-HT3 receptor-mediated ion current in NCB-20 neuroblastoma cells. 171 59

Whole cell and patch clamp techniques were used to investigate the properties of 5-HT3 receptors of a murine neuroblastoma cell line (N1E-115) and adult rabbit nodose ganglion neurones. In addition, some preliminary results from guinea-pig nodose ganglion neurones are presented. In such cells, voltage-clamped at -60 mV, 5-HT (10 microM) induced an inward current associated with a conductance increase. The results of ion substitution experiments suggest that the 5-HT activated ion channel is permeable to both Na+ and K+ ions with a permeability ratio (PNa/PK) of 0.94 and 0.92 for rabbit nodose ganglion cells and N1E-115 cells respectively. On outside out membrane patches excised from rabbit nodose ganglion neurones, 5-HT (1 microM) activated clearly discernible single channel currents with a conductance of 16.6 +/- 0.7 pS (n = 4). In contrast, fluctuation analysis of 5-HT induced whole cell currents suggests that the single channel conductance of N1E-115 cells is only 0.3 pS, a value some 50 fold lower. The 5-HT-induced whole cell currents recorded from all three preparations were antagonised by the selective 5-HT3 receptor antagonist ondansetron (GR38032F) and by the less selective agents metoclopramide, cocaine and (+)-tubocurarine. However, these preparations demonstrate a differential sensitivity to some antagonists. In particular, (+)-tubocurarine was a potent antagonist in N1E-115 cells (IC50 = 0.85 nM) but was approximately 200 fold (IC50 = 156 nM) and 1200 fold (IC50 = 10 microM) less potent in rabbit and guinea-pig nodose ganglion neurones respectively. Additionally, a novel effect of ketamine (10 microM) to potentiate the 5-HT-induced current of rabbit nodose ganglion neurones is described.
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PMID:Physiological and pharmacological properties of 5-HT3 receptors--a patch clamp-study. 171 28

1. The effects of 5-HT3 selective agonists have been studied in whole-cell voltage-clamped N1E-115 neuroblastoma cells. 2. Application of 5-hydroxytryptamine (5-HT) results in the rapid development of a transient inward current at quasiphysiological membrane potentials. This current can be blocked by the 5-HT3 specific antagonists BRL 43694 and GR67330. 3. Application of 2-methyl-5-HT (2-Me5-HT), a 5-HT3 selective agonist, produced a qualitatively similar inward current, but with a maximum response only 20% of that produced by 5-HT. 4. In the presence of 100 microM 2-Me5-HT, the upper part of the 5-HT dose-response curve was shifted to the right but reached the same maximum value as in the absence of 2-Me5-HT. 2-Me5-HT appears therefore to be a partial agonist under these conditions. 5. The novel 5-HT3 agonist, meta-chlorophenylbiguanide (mCPBG) is a full agonist, but has a Hill coefficient (1.5) significantly less than that of 5-HT (2.3). 6. Comparison with radioligand binding data show that mCBPG is 100 times less potent than expected; it may therefore exhibit a high affinity for a desensitized state.
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PMID:The agonist properties of m-chlorophenylbiguanide and 2-methyl-5-hydroxytryptamine on 5-HT3 receptors in N1E-115 neuroblastoma cells. 179 17


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