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 activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma--brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of NIE-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and NIE-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that (i) NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, (ii) activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and (iii) serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.
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PMID:Adenylate cyclase and acetylcholine release regulated by separate serotonin receptors of somatic cell hybrids. 22 Jun 7

GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the serotonin (5-HT) uptake inhibitor alaprocalate but without effects on the 5-HT uptake, was shown to potentiate muscarinic cholinergic responses in N1E-115 neuroblastoma cells. In intracellular recording experiments, GEA 857 (1 microM) increased the cell input resistance and prolonged the action potential. It also prolonged the cellular response to carbachol acting on muscarinic receptors in a manner mimicked by potassium channel blockers such as 4-aminopyridine and TEA. GEA 857 did not affect the carbachol stimulated uptake of 45Ca, but depressed the carbachol activated outflow of 86Rb from neuroblastoma cells. The conclusion drawn from these results is that GEA 857 reduces potassium conductances in the membrane in N1E-115 neuroblastoma cells and, thereby, prolongs muscarinic agonist-induced responses.
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PMID:GEA 857 blocks potassium channels in the membrane and, thereby, prolongs muscarinic cholinergic responses in N1E-115 neuroblastoma cells. 130 Oct 72

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

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

5-HT3 receptor-mediated membrane currents were recorded from voltage-clamped clonal N1E-115 neuroblastoma cells. The inward current response to ionophoretically applied serotonin (5-HT) was reversibly antagonised by the 5-HT3 receptor antagonists GR 38032F and metoclopramide with IC50 values of 0.2 nM and 14 nM, respectively. Low concentrations of (+)-tubocurarine [+)-Tc) also blocked the response to 5-HT (IC50 = 0.8 nM), but other nicotinic cholinoceptor antagonists (gallamine, vecuronium and trimetaphan) were ineffective when applied at a relatively high concentration (1 microM). Blockade by (+)-Tc was neither voltage- nor use-dependent, suggesting that (+)-Tc does not block 5-HT-activated ion channels in N1E-115 cells.
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PMID:Antagonism of 5-HT3 receptor mediated currents in murine N1E-115 neuroblastoma cells by (+)-tubocurarine. 169 68

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

Recent studies indicate that ethanol (EtOH) potentiates ion current through the channel associated with the 5-hydroxytryptamine3 (5-HT3)-type serotonin receptor. The present study was designed to determine 1) whether such potentiation occurs in adult mammalian neurons expressing 5-HT3 receptors; 2) whether potentiation is selective for the 5-HT3 receptor, relative to other ligand-gated ion channels; and 3) possible mechanisms by which EtOH potentiates this response. EtOH potentiated 5-HT3 receptor-mediated ion current in freshly isolated nodose ganglion neurons at concentrations similar to those previously reported to be effective in neuroblastoma cells (25-100 mM). Current was blocked by the selective 5-HT3 antagonist ICS 205-930 even in the presence of EtOH, and current activated by a 5-HT3 agonist (2-methyl-5-HT) was potentiated by EtOH. Thus, EtOH appears to produce potentiation via an alteration in the function of 5-HT3 receptors and not through an independent effect. gamma-Aminobutyric acidA receptor-mediated Cl- current was not potentiated by EtOH in neurons in which potentiation of responses to 5-HT was observed. Methanol potentiated 5-HT3 receptor-mediated current with a potency lower than that of EtOH. Potentiation by EtOH decreased with increasing 5-HT concentration. In addition, EtOH increased the decay rate of current. EtOH did not alter the reversal potential of the 5-HT3 receptor-mediated current. These observations indicate that intoxicating concentrations of EtOH selectively potentiate 5-HT3 receptor-mediated responses by increasing the apparent potency of 5-HT for activating ion current.
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PMID:Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. 171 16

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

The neurotransmitter serotonin (5HT) activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. Serotonin also activates ion channels directly, suggesting that it may also mediate rapid, excitatory responses. A complementary DNA clone containing the coding sequence of one of these rapidly responding channels, a 5HT3 subtype of the serotonin receptor, has been isolated by screening a neuroblastoma expression library for functional expression of serotonin-gated currents in Xenopus oocytes. The predicted protein product has many of the features shared by other members of the ligand-gated ion channel family. The pharmacological and electrophysiological characteristics of the cloned receptor are largely consistent with the properties of native 5HT3 receptors. Messenger RNA encoding this receptor is found in the brain, spinal cord, and heart. This receptor defines a new class of excitatory ligand-gated channels.
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PMID:Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. 171 42

IMR-32 and SK-N-MC cells were found to contain [3H]quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable [3H]8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC50 value of about 50 microM in both cases. Pirenzepine inhibited the carbachol (100 microM)-stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC50 values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT1A receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA2 values of 5.78 (IMR-32) and 5.61 (SK-N-MC). These values are consistent with the inhibitory potency of 8-OH-DPAT towards [3H]quinuclidinyl benzilate binding in these cells. The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT (10-100 microM) was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.
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PMID:Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells. 182 86


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