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)

Serotonin (5-HT) induced a transient rise of the cyclic GMP level in neuroblastoma X glioma hybrid cells, half-maximally at 1 microM 5-HT. 2-Methyl-5-HT displayed an about 5 times lower potency but equal efficacy. alpha-Methyl-5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were completely ineffective at concentrations up to 30 microM. Antagonists specific for 5-HT3 receptors, ICS 205-930, GR 38032 F and MDL 72222, blocked the response to 5-HT at nanomolar concentrations but antagonists directed towards 5-HT1 and 5-HT2 receptors, ketanserin and methysergide, had no effect at concentrations up to 1 microM. Thus, 5-HT3 receptors are responsible for activating guanylate cyclase in the hybrid cells.
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PMID:Serotonin raises the cyclic GMP level in a neuronal cell line via 5-HT3 receptors. 254 82

The mechanisms of action of two different serotonin receptors, found in a neuronal cell line (neuroblastoma X glioma hybrid cells) and in a non-excitable glioma cell line, were explored. In both cell lines, serotonin induced a dose-dependent, transient rise of cytosolic Ca2+ activity (measured by fura-2 or indo-1 fluorescence). Ca2+ channel blockers (Ni2+ and La3+, not nifedipine) suppressed the Ca2+ response to serotonin in the hybrid cells but not in the glioma cells. After application of Ca2+ ionophores (ionomycin and A23187) in order to short-circuit internal Ca2+ stores, serotonin was still able to induce a Ca2+ response in the hybrid cells but not in the glioma cells. Serotonin dose-dependently stimulated the rate of 45Ca2+ uptake several-fold in the hybrid cells, but hardly at all in the glioma cells. Thus, in the neuronal cell line cytosolic Ca2+ activity is raised through enhancement of Ca2+ entry into the cells from the extracellular environment via 5-HT3 receptors (blocked by ICS 205-930, MDL 72222 and GR 38032 F). The depolarization response caused by serotonin in the hybrid cells is due to activation of cation conductance(s), obviously allowing entry of extracellular Ca2+. In contrast to the neuronal cell line, in the glial cell line the rise of Ca2+ activity is mediated by ketanserin-susceptible 5-HT2 receptors (not affected by treatment with pertussis toxin) mainly liberating Ca2+ from internal stores. In the glioma cells the release of Ca2+ from internal stores leads to opening of Ca2+-dependent K+ channels, responsible for the hyperpolarizing response. Thus, the neuronal and the glial cell lines might provide suitable systems in which to study the diverse cellular functions triggered by the rise of cytosolic Ca2+ activity, which is caused by different serotonin receptors.
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PMID:Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 5-HT3 and 5-HT2 receptors by different mechanisms. 260 42

Specific binding sites for [3H]zacopride were found in the dorsal part of the rat spinal cord, particularly in the superficial layers of the dorsal horn. These binding sites had the same pharmacological profile as 5-HT3 receptors in membranes from the rat entorhinal cortex or from NG 108-15 neuroblastoma-glioma cells. Administration of capsaicin (50 mg/kg s.c.) to neonatal rats to induce degeneration of unmyelinated primary sensory fibres resulted in a significant decrease in [3H]zacopride specific binding (-50%) in the dorsal zone of the spinal cord of 4 month-old rats. This decrease was as pronounced as the decrease in [3H]bremazocine and [3H]naloxone binding to opiate receptors. These data support the presynaptic location of 5-HT3 receptors, at least in part, on capsaicin-sensitive primary afferent fibres in the rat spinal cord.
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PMID:5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. 275 79

[3H]ICS 205-930 labelled 5-HT3 recognition sites in membranes prepared from murine neuroblastoma N1E-115 cells. Binding was rapid, reversible, saturable and stereoselective to an apparently homogeneous population of sites. Kinetic studies revealed that agonists and antagonists produced a monophasic dissociation reaction of [3H]ICS 205-930 from its recognition sites. The dissociation rate constant of the radioligand was similar whether the dissociation was induced by an agonist or an antagonist. Competition studies carried out with agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were best fit for a 1 site model. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. The interactions of agonists and antagonists with [3H]ICS 205-930 recognition sites were apparently competitive in nature, as demonstrated in kinetic and equilibrium experiments. In saturation experiments carried out with [3H]ICS 205-930 in the presence and the absence of unlabelled agonists and antagonists, apparent Bmax values were not reduced whereas apparent Kd values were increased in the presence of competing ligands. There was a good agreement between apparent pKB values calculated for the competing ligands in saturation experiments and pKd values calculated from competition experiments. The present data demonstrate that [3H]ICS 205-930 labels a homogeneous population of sites at which agonists and antagonists interact competitively.
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PMID:Competitive interaction of agonists and antagonists with 5-HT3 recognition sites in membranes of neuroblastoma cells labelled with [3H]ICS 205-930. 291 46

[3H]ICS 205-930 recognition sites were analyzed in membranes prepared from murine neuroblastoma N1E-115 cells. [3H]ICS 205-930 bound rapidly, reversibly, and stereoselectively to a homogeneous population of high affinity recognition sites: Bmax = 40 +/- 5 fmol/mg of protein, pKD = 9.20 +/- 0.05 (n = 11). Nonlinear regression and Scatchard analysis of saturation data suggested the existence of a single class of [3H]ICS 205-930 recognition sites on N1E-115 cells. The affinity of [3H]ICS 205-930 determined in kinetic studies was in agreement with that obtained under equilibrium conditions. Competition studies carried out with a large variety of agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. [3H]ICS 205-930-binding sites displayed the pharmacological profile of a 5-HT3 receptor. Potent 5-HT3 receptor antagonists showed nM affinities for [3H]ICS 205-930-binding sites with the following rank order of potency: SDZ 206-830 greater than SDZ 206-792 greater than ICS 205-930 greater than BRL 43694 greater than quipazine greater than BRL 24924 greater than MDL 72222 greater than GR 38032F. Methiothepine, mCPP, and metoclopramide showed sub-microM affinity. The rank order of potency of agonists was: 5-HT greater than phenylbiguanide = 2-methyl-5-HT much greater than 5-methoxytryptamine = 5-carboxamidotryptamine. All antagonist competition curves were steep (pseudo-Hill coefficients not lower than 1), monophasic, and best fit for a one-site model; 5-HT and 2-methyl-5-HT produced pseudo-Hill coefficients of 1.2-1.4. Drugs acting at 5-HT1, 5-HT2, alpha- and beta-adrenergic, dopaminergic, and histaminergic receptors (methysergide, ketanserin, propranolol, phentolamine, sulpiride, SCH 23390, cimetidine) were essentially inactive at 10 mumol/liter. The binding of [3H]ICS 205-930 was not affected by guanine and adenine nucleotides (GTP, GppNHp, and ATP) at 1 mmol/liter. These nucleotides did not affect the binding of agonists, suggesting that 5-HT3 recognition sites are not coupled to G-proteins. The interactions of agonists and antagonists with [3H]ICS 205-930 recognition sites were competitive in nature, as demonstrated by saturation experiments carried out with [3H]ICS 205-930 in the presence and the absence of unlabeled compounds: apparent Bmax values were not reduced, whereas apparent KD values were increased in the presence of competing ligands.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding. 335 95

The influence of memantine on several properties of a neuronal cell line was tested. The aim was to get some insight into possible mechanisms of action of this drug which is therapeutically applicable in treatment of spasticity, Parkinson's disease, and cerebral coma. In neuroblastoma X glioma hybrid cells, memantine, at micromolar concentrations, blocked the depolarization induced by iontophoretically applied serotonin (5-hydroxytryptamine, 5-HT). In the hybrid cells, receptors of the 5-HT3 type mediated the depolarization, which was frequently accompanied by a series of action potentials. The inhibition by memantine of the serotonin response occurred fast and was completely reversible, irrespective of whether the cell showed a stable membrane potential or spontaneous action potentials. However, memantine did not alter spontaneous or electrically evoked action potential activity in the hybrid cells, and apparently did not block the underlying ionic conductances. Furthermore memantine did not affect either the cation permeability activated by substance P in the hybrid cells or the K+ channel triggered by bradykinin in a glioma cell line. Thus, memantine appears specifically to suppress the ion channel opened by serotonin in the hybrid cells. The interaction of memantine with serotonin receptors and the associated ion channels reported here, might give an important clue, as to a site of action of memantine in the nervous system.
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PMID:Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line. 335 74

The aim of this study was to investigate the pharmacological characteristics of the 5-hydroxytryptamine-(5-HT)-induced electrical response in cultured neuroblastoma N1E-115 cells of the mouse. In these cells 5-HT induces a transient membrane depolarization, which is associated with a transient inward current, that has been recorded in voltage clamp experiments on whole cells. The peak amplitude of the inward current depends on the concentration of 5-HT applied. Maximum peak inward current was evoked by 10 microM 5-HT and half maximum effect by 2 microM. Responses to 5-HT were blocked by nanomolar concentrations of selective 5-HT3-receptor antagonists, whereas the selective agonist 2-methyl-5-HT mimicked the membrane depolarization induced by 5-HT. A number of agonists and antagonists, which are known to act on 5-HT1-like, 5-HT2, dopaminergic and adrenergic receptors failed to affect the response to 5-HT in neuroblastoma cells. Observed antagonistic effects of SCH 23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol hemimaleate] and haloperidol are discussed. The inhibitory effect of the 5-HT3 receptor antagonist, ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester] has been demonstrated. When cells were exposed to 0.1 nM ICS 205-930 the maximum evoked response was reduced by about 50%, but a surmountable shift of the concentration-response curve of 5-HT was not observed. The kinetics of the 5-HT-induced inward current remained unchanged in the presence of ICS 205-930. Recovery from the block by ICS 205-930 was very slow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of serotonin 5-HT3 receptor-mediated electrical response in cultured mouse neuroblastoma cells. 337 70

Whole cell and outside-out patch clamp recordings were obtained from primary cultures of rat and mouse hippocampal neurons. Serotonin (5-HT) evoked short-latency fast inward currents in about 5% of neurons. These currents reversed near 0 mV, showed inward rectification, and were inhibited by the 5-HT3 receptor antagonists ICS 205-930, ondansetron and tubocurare. 5-HT activated single channel currents in 14 of 24 membrane patches obtained from neurons which showed 5-HT3-activated whole cell currents; mean amplitude of channel openings was 0.95 +/- 0.09 pA at -100 mV. Chord conductances measured at -80 and -160 mV were 8.3 and 10.5 pS, respectively. 5-HT-induced unitary currents were blocked reversibly by tubocurare (1 microM), ICS 205-930 (30 nM) and ondansetron (100 nM). Thus, single-channel properties of 5-HT3 receptors in hippocampal neurons are similar to those present in peripheral neurons and do not exhibit solely the sub-picosiemen conductance characteristic of the neuroblastoma and neuroblastoma-derived cloned 5-HT3 receptor.
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PMID:Single channel properties of the 5-HT3 subtype of serotonin receptor in primary cultures of rodent hippocampus. 752 84

The anti-hypertensive drug ifenprodil is known to interact potently with the alpha 1-adrenergic receptor as well as a number of other second messenger-linked receptors. In addition to these properties, ifenprodil has been shown to prevent glutamate-mediated excitotoxicity via non-competitive antagonism of NMDA receptors [Legendre and Westbrook (1991) Molec. Pharmac. 40: 289-298; Shalaby et al. (1992) J. Pharmac. Exp. Ther. 260: 925-932]. With these things in mind, we have begun to examine the specificity of ifenprodil for various ligand-gated ion channels using electrophysiological methods. While ifenprodil effectively inhibits NMDA-mediated currents in cortical neurons in culture, it does not interact with either kainate or GABA receptors. Surprisingly, ifenprodil also acts as a relatively potent antagonist of the 5-hydroxytryptamine3 (5-HT3) receptor in the NG108-15 neuroblastoma x glioma cell line. Furthermore, several aspects of ifenprodil action on the 5-HT3 receptor resemble its interaction with the NMDA receptor. Namely, inhibition of 5-HT3-mediated cation currents is readily reversible, has relatively slow onset, is non-competitive, and is not voltage dependent. Since most of the known 5-HT3 antagonists are competitive, it is possible that ifenprodil may define a unique modulatory site(s) on this neurotransmitter receptor.
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PMID:Ifenprodil inhibition of the 5-hydroxytryptamine3 receptor. 756 98

The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT3 receptor antagonist LY278584. Cocaine (0.1 to 10 microM) reversibly inhibited the current activated by 1 microM 5-HT in a concentration-dependent manner. The IC50 value is 0.7 microM and the apparent Hill coefficient is 1.55. This effect of cocaine was not dependent on membrane potential. Cocaine also produced a parallel shift of the 5-HT concentration-response curve to the right and did not reduce the maximal current induced by 5-HT. In the presence of 3 microM cocaine, the EC50 value of 5-HT was increased from 3.08 microM to 6.1 microM. Other local anesthetics such as tricaine and lidocaine also inhibited the current induced by 5-HT. These results suggest that the 5-HT3 receptors expressed in Xenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner.
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PMID:Effect of cocaine on the 5-HT3 receptor-mediated ion current in Xenopus oocytes. 760 30


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