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

The present study has demonstrated the distribution of [3H]granisetron-labelled 5-HT3 receptors in the human forebrain with relatively high levels of this receptor in homogenates of hippocampus, caudate nucleus, putamen, nucleus accumbens and amygdala. Lower levels of 5-HT3 receptors were found in other brain regions and the cervical vagus nerve. Pharmacological characterization of the labelled 5-HT3 receptor in human putamen homogenates identified a relatively low affinity for d-tubocurarine compared to the 5-HT3 receptor in NG108-15 neuroblastoma-glioma cell homogenates. In contrast, the affinities of 19 other 5-HT3 receptor ligands were not significantly different for the [3H]granisetron-labelled receptor in these two preparations. Such findings indicate that the human putamen 5-HT3 receptor displays a unique pharmacology which may have significance given the reported clinical potential of compounds active at this receptor when assessed in animal models of disease.
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PMID:Distribution and characterization of the [3H]granisetron-labelled 5-HT3 receptor in the human forebrain. 815 23

The binding of three, structurally distinct, 5-hydroxytryptamine3 (5-HT3) receptor radioligands was characterized in rat cerebral cortex, rabbit ileum myenteric plexus and NG-108-15 neuroblastoma cells. The density of sites labeled by the three ligands in rat cortex or in rabbit ileum was markedly different. [3H]Quipazine labeled more sites than [3H]GR 65630 in rat cortex (4.0-fold) and rabbit ileum (1.8-fold), but not in NG-108-15 cells. [3H]Quipazine also labeled a greater density of sites than [3H]granisetron in rat cortex (7-fold) but not in NG-108 cells. [3H]Quipazine binding in rat cortex and rabbit ileum, but not in NG-108-15 cells, was displaced by non-radiolabeled GR 65630 in a manner consistent with an interaction with more than one site. These data indicate that not all 5-HT3 receptor radioligands recognize the same population of 5-HT3 binding sites with equivalent density and further suggest the existence of subtypes of 5-HT3 receptor binding sites in rat cortical and rabbit myenteric plexus preparations.
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PMID:Different densities of 5-HT3 receptors are labeled by [3H]quipazine, [3H]GR 65630 and [3H]granisetron. 823 90

The binding characteristics of a radiolabelled 5-HT3 receptor agonist, [3H]meta-chlorophenylbiguanide (mCPBG), were examined in membranes from N1E-115 neuroblastoma cells. Scatchard plots of saturation binding data showed the presence of two populations of binding sites, with Kd = 0.03 +/- 0.01 nM and 4.4 +/- 1.2 nM and Bmax = 11.9 +/- 4.2 and 897.9 +/- 184.7 fmol/mg protein respectively. Competition studies with a selection of agonists and antagonists revealed the pharmacological profile expected for a 5-HT3 receptor. The rank order of potency for antagonists was granisetron > quipazine > GR65630 > ondansetron > MDL72222, and for agonists was mCPBG > 5-HT (5-hydroxytryptamine, serotonin) > 2-methyl-5-HT. IC50 values for 5-HT and 2-methyl-5-HT were lower than those observed using radiolabelled antagonists, and combined with functional experiments, the data suggest that [3H]mCPBG may label high affinity desensitized states of the receptor. We conclude that [3H]mCPBG labels 5-HT3 receptors in N1E-115 neuroblastoma cell membranes and may be a useful compound with which to explore 5-HT3 receptors in other systems.
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PMID:Characterization of [3H]meta-chlorophenylbiguanide binding to 5-HT3 receptors in N1E-115 neuroblastoma cells. 825 26

Previous studies showed that whereas the potent 5-HT3 receptor antagonist (S)-[3H]zacopride only labels 5-HT3 receptor binding sites, the (R)-enantiomer, (R)-[3H]zacopride, labels these receptors and another class of high-affinity binding sites, named the R sites, in membranes from the rat cerebral cortex and NG 108-15 clonal cells (Kidd et al., Eur. J. Pharmacol. 211, 133, 1992). Further studies of R sites revealed that they existed not only in the cerebral cortex but also in various other areas of the rat brain and spinal cord. In addition, R sites were also found in post-mortem human brain tissues. Both in the rat and in man, the regional distribution of central R sites was markedly different from that of 5-HT3 receptors specifically labelled with (S)-[3H]zacopride. Under appropriate conditions for the specific labelling of R sites (with (R)-[3H]zacopride in the presence of 1.0 microM ondansetron to saturate 5-HT3 receptor binding sites--and 0.1 mM mianserin for the determination of non-specific binding), these R sites were also found in rat peripheral tissues (intestine > spleen > kidney > testicles = liver > adrenals > lung > heart). At least in the kidney and the liver, the pharmacological profile of R sites corresponded exactly to that found in NG 108-15 cells. R sites were also detected in membranes from C6 glioma cells and glial cells cultured from the whole cortex of new born rats. In contrast, no specific binding of (R)-[3H]zacopride to R sites could be found in membranes from N1E-115 neuroblastoma cells. Conversely, 5-HT3 receptors could be labelled by (S)-[3H]zacopride in the latter cells but not in C6 glioma and cultured glial cells. As expected from their glial location, the density of R sites increased in the rat hippocampus lesioned with kainic or ibotenic acid to induce local gliosis. In contrast, the density of hippocampal 5-HT3 receptors was unchanged in lesioned rats. Finally, the determination of the apparent molecular size of R sites by radiation inactivation gave a value (approximately 30 kDa) which was significantly lower than that of 5-HT3 receptor binding sites in the rat entorhinal cortex (40 kDa) and NG 108-15 cells (57 kDa). All these data clearly showed that R sites and 5-HT3 receptors are different molecular species. Whether R sites mediate the 5-HT3 receptor-unrelated actions of (R)-zacopride deserves further investigations.
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PMID:Characterisation of the non-5-HT3 high-affinity 'R' binding site for (R)-zacopride in brain and other tissues. 825 60

The effects of the novel antagonist S 11978 (Endo-7-[(8-methyl-8-azabicyclo[3,2,1]-3-octyl)oxycarbonyl] benzo[b] thiophene) on 5HT3 receptors were examined in N1E-115 mouse neuroblastoma x rat glioma hybrid cells, with radioligand binding and whole cell patch clamp techniques. The 5HT3 receptor ligand [3H] quipazine was displaced by ICS 205-930, GR 38032F and S 11978 with KI values of 2.25 nM, 36.5 nM and 1.75 nM respectively. Electrophysiological studies showed that S 11978 is a potent 5HT3 antagonist: IC50 values for inhibition of 5HT-induced inward current by ICS 205-930, GR 38032F and S 11978 were 0.22 nM, 0.63 nM and 0.43 nM respectively at a holding potential of -65 mV. It is concluded that S 11978 is a potent, high affinity 5HT3 receptor antagonist.
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PMID:The antagonist properties of S 11978 on 5HT3 receptors in N1E-115 neuroblastoma cells. 837 May 67

The pharmacological characteristics of 5-HT3 receptor (5-hydroxytryptamine3 receptor) recognition sites labelled with [3H]-(S)-zacopride and [3H]granisetron in membranes prepared from NG108-15 neuroblastoma-glioma cells were directly compared to investigate further differences in the binding characteristics of these two radioligands. Competition curves generated with increasing concentrations of 5-HT3 receptor ligands emphasized the pharmacological similarity of the two recognition sites labelled by [3H]-(S)-zacopride and [3H]granisetron. However, analysis of the nature of the competition curves indicated that 5-HT3 receptor agonists (5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, phenylbiguanide) and quipazine generated Hill coefficients greater than unity when the 5-HT3 receptor recognition sites were labelled with [3H]granisetron whilst these competing compounds displayed Hill coefficients of around unity when the sites were labelled with [3H]-(S)-zacopride. Competition for either [3H]-(S)-zacopride or [3H]granisetron binding by the 5-HT3 receptor antagonists granisetron and ondansetron generated Hill coefficients around unity. Furthermore, addition of unlabelled (S)-zacopride (1.0 nM) failed to alter the nature by which quipazine competed for the [3H]granisetron-labelled 5-HT3 receptor recognition site. Consistent with 5-HT3 receptors radiolabelled in rat cortical membranes, the present studies indicate that [3H]-(S)-zacopride may label a different site on the 5-HT3-receptor complex compared to [3H]granisetron.
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PMID:Differential binding characteristics of agonists at 5-HT3 receptor recognition sites in NG108-15 neuroblastoma-glioma cells labelled by [3H]-(S)-zacopride and [3H]granisetron. 839 Feb 63

The effect of a novel 5-HT3 receptor antagonist, BRL 46470, has been studied on two electrophysiological models for 5-HT3 receptors: grease-gap recordings from rat isolated vagus nerve and whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma NG108-15 cells. Its action on the rat vagus nerve was compared to that of four other 5-HT3 receptor antagonists. On the rat vagus, BRL 46470 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner with an IC50 of 0.3-1.0 nM, but the EC50 for 5-HT was not appreciably affected. This action was similar to that of granisetron and ICS 205-930, but differed from that of GR38032F and (+)-tubocurarine which produced clear rightward shifts of the concentration-response curve to 5-HT. The 5-HT-induced fast inward current of voltage-clamped NG108-15 cells was also antagonized by 1 nM BRL 46470 in an insurmountable manner. In contrast to (+)-tubocurarine, the action of BRL 46470 on the rat vagus nerve and NG108-15 cells did not readily reverse on washing with antagonist-free medium. It is concluded that BRL 46470 is a potent, insurmountable 5-HT3 receptor antagonist on the rat vagus and NG108-15 cells.
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PMID:BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors. 841 36

Single 5-HT3 receptor-gated ion channels were recorded in cell-attached and excised membrane patches of mouse N1E-115 neuroblastoma cells. In cell-attached patches 5-HT3 receptor-gated ion channels show distinct conductance levels of 27, 18, 11 and 6 pS. Patch excision, buffering of intracellular Ca2+ by BAPTA and inhibition of protein kinase activity by staurosporine increase the probability of occurrence of the 6 pS level and decrease that of the 27 pS level. Conversely, patch cramming and stimulation of protein kinase activity by the phorbol ester PMA enhance the probability of occurrence of the 27 pS level and decrease that of low conductance levels. We conclude that phosphorylation controls the conductance of 5-HT3 receptor ligand-gated ion channels. Control of channel conductance may prove an additional mechanism in the modulation of synaptic efficacy.
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PMID:Phosphorylation controls conductance of 5-HT3 receptor ligand-gated ion channels. 858 95

Two splice variants of the ligand-gated 5-hydroxytryptamine or serotonin 5-HT3 receptor that differ in a six-amino-acid deletion were cloned by polymerase chain reaction from the hippocampus x neuroblastoma cell line HN9.10e. When expressed in Xenopus oocytes, both variants individually formed 5-HT3 receptors that revealed no significant differences in current responses to the agonists 5-HT and 1-phenylbiguanide and block by the specific antagonist LY-278, 584-maleate. For both receptors, the monovalent cations Na+, K+, Rb+ and Li+ showed the same relative permeability; NH4(+)permeated approximately 2.7 times better than Na+, and Tris+ was only poorly permeable. In contrast to other reports, the receptors were completely and reversibly blocked by extracellular Cs+ in both oocytes and native HN9.10 cells. Moreover, Ca2+ was not permeant and exhibited a concentration-dependent decrease (0.9-18 mM) of the 5-HT-induced currents without affecting the inward rectification of the current/voltage relation. The two receptors were reversibly inhibited by nanomolar concentrations of the specific inhibitor of protein kinase C (PKC) bisindolylmaleimide, but not by the equipotent and less specific inhibitor staurosporine. A regulatory effect on both 5-HT3 receptor subunits by PKC-mediated protein phosphorylation might be possible, however, a functional role of the two splice variants present in one cell remains to be determined.
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PMID:Functional characterization of two 5-HT3 receptor splice variants isolated from a mouse hippocampal cell line. 866 78

1. NIE-115 mouse neuroblastoma cells were studied under voltage clamp in the whole-cell patch-clamp configuration. Peak currents induced by bath application of 5-hydroxytryptamine (5-HT) were inwardly rectifying, reversed at 0.4 +/- 0.2 mV (mean +/- s.e.mean), and were approximately half-inhibited (at 1 microM 5-HT) by 2 nM of the 5-HT3 selective antagonist MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). 2. Peak inward currents activated by a low concentration of 5-HT at a holding potential of -50 mV were potentiated by volatile general anaesthetics. At their human minimum alveolar concentrations (MACs), the degree of potentiation increased in the order isoflurane < halothane < enflurane < methoxyflurane. Potentiation by methoxyflurane was independent of membrane potential in the range -70 mV to +40 mV. The reversal potential was the same in the presence and absence of methoxyflurane. 3. Methoxyflurane shifted the 5-HT dose-response curve to lower 5-HT concentrations, without significantly changing the Hill coefficient or maximum response. The EC50 concentration for 5-HT decreased from 1.86 +/- 0.02 microM to 1.07 +/- 0.11 microM (means +/- s.e.mean) due to the presence of 1 MAC (270 microM) methoxyflurane. 4. In contrast to the volatile anaesthetics, the barbiturate anaesthetic, thiopentone, inhibited the 5-HT3 receptor. Hill analysis of thiopentone dose-response data gave an average IC50 = 117 +/- 8 microM thiopentone and Hill coefficient = 1.6 +/- 0.2 (means +/- s.e.mean). These parameters were not significantly different for data obtained at 5-HT concentrations above and below the control EC50 concentration for 5-HT, consistent with non-competitive inhibition. 5. The n-alcohols occupied an intermediate position between the volatile and barbiturate anaesthetics. The lower alcohols (butanol and hexanol) potentiated 5-HT responses at low alcohol concentrations but inhibited them at high concentrations. In contrast, the higher alcohols (octanol, decanol, dodecanol, tridecanol, tetradecanol and pentadecanol) produced no potentiation, but only inhibition, at all alcohol concentrations. 6. Inhibition of the 5-HT3 receptor by the n-alcohols exhibited a cutoff in potency similar to those previously found for tadpoles, luciferase enzymes and a neuronal nicotinic acetylcholine receptor channel.
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PMID:Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells. 873 Jul 47


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