Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on commonalities between peripheral blood "immunocytes" and central nervous system cells (both have receptors for endorphins, enkephalins, dopamine, acetylcholine, etc.) blocking of potassium ion channels in both brain cell synaptosome and suppressor T cells, and common sharing of antigenic determinants on one or another immunocyte and one or another CNS cells, we postulated that peripheral blood immunocytes can be used to study CNS mechanisms. In the present studies we used peripheral blood lymphocytes to study the effects of phencyclidine (PCP) on various receptors. This agent causes a permanent psychosis similar to chronic schizophrenia in a small percent of users. We observed similar effects in binding to sigma receptors, inhibition of binding and reversibility of binding in receptors of both human peripheral blood receptors and the mouse neuroblastoma, a hamster brain cell hybrid clone. The results are complete with the hypothesis that some cases of schizophrenia are immunologically mediated, perhaps due to antibodies to the sigma receptor. Alternatively, immunologic deficiency might hinder elimination of neurotropic viruses which in genetically predisposed individuals bind to and block the sigma receptor. Functional deficiency of the brain cell equivalent of lymphocyte suppressor T cells by one or another immunologic mechanisms or an excess of T helper cells might also cause schizophrenia by causing an excess of normal brain "B-cell equivalent cell" output response to sensory input.
 ...
PMID:Sigma receptors and autoimmune mechanisms in schizophrenia: preliminary findings and hypotheses. 609 18

The neurotoxic action of toxin gamma from the venom of the Brazilian scorpion Tityus serrulatus (TiTx gamma) has been investigated in cultured mouse neuroblastoma cells (N1E115) using the suction pipette technique. Addition of 14 to 53 nM TiTx gamma to the external solution causes nerve cell membrane depolarization, membrane potential oscillations and spontaneous action potentials within 10 min. None of these effects were observed within 15 min after application of 1 microM toxin IV from Centruroides sculpturatus venom. Under voltage clamp the amplitude of the sodium current evoked by test pulses to potentials more positive than -30 mV is reversibly reduced by 50% after 17 to 105 nM TiTx gamma. On the other hand, a sodium current component appears after TiTx gamma at test pulse potentials between -70 and -40 mV, for which no sodium current is observed in the control experiment. The outward potassium current is not significantly affected by the highest TiTx gamma concentrations used. The potential-dependence of inactivation of the sodium current component that is induced by TiTx gamma is shifted by -30 mV with respect to control values. The local anaesthetic procain at 1 mM discriminates between the two populations of sodium channels observed in the presence of TiTx gamma.
 ...
PMID:A new scorpion toxin with a very high affinity for sodium channels. An electrophysiological study. 609 13

Tyrosine hydroxylase (TH) activity is increased two- to threefold in neuroblastoma cell line NBP2 maintained in culture for 48 h in the presence of either the inhibitor of cyclic AMP-phosphodiesterase (PDE), 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724), or the activator of adenylate cyclase, prostaglandin E1 (PGE1). Cyclic AMP levels are elevated 70-80% and 30-40% throughout the 48-h treatment with RO 20-1724 and PGE1, respectively. Carbachol does not affect either basal TH activity or cyclic AMP levels in the cells. However, the cholinergic agonist delays the induction of TH elicited by either RO 20-1724 or PGE1. This delay is prevented by atropine. The elevation in cyclic AMP levels elicited by either RO 20-1724 or PGE1 is blocked for 1 h or 15 min, respectively, after treatment with carbachol. Cyclic AMP levels then begin to rise until they reach those levels observed in the presence of RO 20-1724 or PGE1 alone by 12 h or 1 h of treatment, respectively. Time course studies demonstrate that this transient inhibition of the elevation of cyclic AMP is associated with a 48-h delay in the induction of TH elicited by either RO 20-1724 or PGE1. In contrast, the induction elicited by 8-bromo cyclic AMP is unaffected by carbachol. A depolarizing concentration (56 mM) of KCl produces a 24-h delay in the induction of TH elicited by RO 20-1724, without affecting the concomitant elevation of cyclic AMP produced by the PDE inhibitor. Furthermore, 56 mM-KCl inhibits the induction of TH elicited by 8-bromo cyclic AMP. It thus appears that carbachol delays the induction of TH by transiently inhibiting the elevation of cyclic AMP, whereas potassium depolarization delays the induction of TH by inhibiting a process with a site of action that is distal to the elevation of cyclic AMP.
 ...
PMID:Effect of carbachol and 56 mm-potassium chloride on the cyclic AMP-mediated induction of tyrosine hydroxylase in neuroblastoma cells in culture. 610 63

The method of intracellular perfusion and voltage clamp was used to investigate potassium channels in the somatic membrane of the rat spinal ganglion neurons and mouse neuroblastoma cell. It is shown that potential-dependent properties of potassium channels in both types of membranes are similar while time constants of activation and inactivation are substantially higher in the neuroblastoma cells. The density of potassium channels was ten times less in the neuroblastoma cells than in the spinal ganglion neurons.
 ...
PMID:[Comparative analysis of the characteristics of potassium channels in the membranes of spinal ganglion neurons and neuroblastoma cells]. 624 60

Phenytoin (diphenylhydantoin) inhibits the calcium-dependent increases in guanosine 3':5'-monophosphate (cGMP) produced by high potassium depolarization and by muscarinic receptor activation in N1E-115 neuroblastoma cells. The inhibition of the cGMP response to depolarization is half-maximal at 40 microM, similar to the plasma concentration associated with an optimal therapeutic response. The cGMP increase produced by the cationophore A23187 is insensitive to phenytoin blockade, indicating that the enzymatic machinery responsible for calcium-stimulated cGMP accumulation is not affected. The calcium concentration-response curve for the cGMP response to high potassium showed that phenytoin acted primarily to reduce the maximal response. The corresponding curve for the cGMP response to acetylcholine showed apparent competitive inhibition by phenytoin whereas the acetycholine concentration-response curve showed noncompetitive inhibition by phenytoin. The results suggest that phenytoin inhibits cGMP responses by blocking calcium influx. The ability to block the depolarization-induced cGMP response is shared by other anticonvulsants which are effective against generalized tonic-clonic and cortical focal seizures but not by those effective against absence seizures.
 ...
PMID:Phenytoin inhibition of cyclic guanosine 3':5'-monophosphate (cGMP) accumulation in neuroblastoma cells by calcium channel blockade. 625 31

Ionic currents of cells of neuroblastoma clone N18 A-1 was studied under conditions when the internal medium was placed for artificial fluoride or phosphate solutions. The specific membrane leakage resistance was measured to be 8.1 +/- 2.6 kOhm.cm2 and 1.3 +/- 0.3 Kohm.cm2, respectively. The presence of usual sodium and tetraethylammonium sensitive potassium channels is demonstrated. Potassium conductance is shown to amount to 0.25--0.025 of sodium conductance. Dialysis of the cells by phosphate solutions induces a slow outward current, which is not inhibited by tetraethylammonium ions.
 ...
PMID:[Ionic currents of neuroblastoma clone N18 A-1 cultured cells under potassium fluoride and phosphate intracellular dialysis]. 625 43

Effects of arachidonic acid on cellular metabolism, cation content, lipid peroxidation, sodium pump activities and release of labeled arachidonic acid were studied in C-6 glioma cells and N18TG2 neuroblastoma cells. Arachidonic acid caused a significant increase in intracellular sodium levels concomitant with a decrease in intracellular potassium in both cell lines. Both (Na+ + K+)-ATPase and p-nitrophenyl phosphatase of glioma cells were inhibited by arachidonic acid whereas only the p-nitrophenyl phosphatase of neuroblastoma cell was inactivated. Low concentrations of arachidonic acid stimulated lactic acid release whereas high concentrations had an opposite effect. In addition, the lipid peroxide content of glioma cells was increased abruptly by 50 microM arachidonic acid whereas only a slight increase of malondialdehyde was observed in neuroblastoma cells. When the cultured cells of both cell lines were incubated with exogenous labeled arachidonic acid, 78-95% of the label was incorporated into membrane phospholipids. Only a very small fraction of prostaglandin E2 and prostaglandin F2 alpha was synthesized. Exogenous arachidonic acid and free radicals generated with xanthine-xanthine oxidase caused a significant release of endogenous labeled arachidonic acid from cellular membrane phospholipids. These data further support our hypothesis that the arachidonic acid and its oxygen radical metabolites induce pathological alterations in membrane permeability and cellular volume.
 ...
PMID:Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells. 628 88

The influence of cycloheximide on currents through sodium and potassium channels in dialysed neuroblastoma cells of clone N18A-1 has been studied under voltage clamp conditions. When cells are incubated with cycloheximide, the conductance of sodium decreases, whereas that of potassium changes only slightly, if at all. The cycloheximide concentration, at which sodium conductance is reduced by 50% during 24 hours incubation, was about 0.5 microgram/ml. The half-time of inhibition at the concentration of 15 microgram/ml was about 9 hours, with the time of 50% inhibition of sodium being more complex than single exponential. The density of sodium channels in control and after the maximal inhibition was estimated to be about 25 and 2.2 micron-2, respectively. The sodium-potassium selectivity and the gating mechanism parameters were shown to be unchanged following cycloheximide treatment.
 ...
PMID:[Turnover of potential-dependent ion channels in the membrane of neuroblastoma cells studied using the protein synthesis inhibitor cycloheximide]. 629 Dec 1

The effects of methylmercury on a variety of electrophysiological properties of the N1E-115 neuroblastoma cells were studied using microelectrode and voltage clamp techniques. The action potential was reduced in amplitude with an apparent dissociation constant of the order of 20 microM in the face of relatively small membrane depolarization. Voltage clamp experiments revealed that both peak sodium current and steady-state potassium current were suppressed by 20-60 microM methylmercury, with a stronger effect on the sodium current than on the potassium current. The protein reagents dithiodipyridine and N-ethylmaleimide suppressed both currents. Acetylcholine receptor/channel complexes are vulnerable to the action of methylmercury; the nicotinic fast depolarizing response, the muscarinic hyperpolarizing response, and the muscarinic slow depolarizing response, were all suppressed by 10-30 microM methylmercury. In contrast, the dopamine induced response was not affected by methylmercury at 30 microM. It was concluded that methylmercury impairs both sodium and potassium channel gating mechanisms and suppresses acetylcholine receptor/channel complexes. It remains to be seen whether the effect of chronic exposure is similar to that seen after acute and high level exposure in the present study.
 ...
PMID:Effects of methylmercury on electrical responses of neuroblastoma cells. 630 85

The effect of cycloheximide (an inhibitor of protein synthesis) on the ionic currents through sodium and potassium channels was investigated in dialysed voltage-clamped N18 A-1 neuroblastoma cells. The cycloheximide concentration needed for half-inhibition of sodium peak conductance was about 0.5 micrograms/ml for 24 h of incubation. Half-inhibition time of the sodium peak conductance in cells incubated with 15.0 micrograms/ml of cycloheximide was about 9 h. Sodium against potassium ion selectivity, the activation and inactivation parameters were shown to be not affected by cycloheximide. Potassium conductance in similarly treated cells exhibited no consistent changes. The main conclusion is that the decay in peak sodium conductance is caused by diminishing the sodium channel density in the membrane (from 25 to 2.2 channels per micron2). The inhibition effect was evidently mediated by block of protein synthesis and was not the result of direct drug-channel interaction. The half-decay time of sodium peak conductance is interpreted as a possible life-time characteristic of sodium channels in the neuroblastoma cell membrane.
 ...
PMID:Effect of cycloheximide on ionic channels in neuroblastoma cell membrane. 631 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>