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)

Four neurotoxins that activate the action potential Na+ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin, a specific inhibitor of the action potential Na+ current, inhibits activation by each of these toxins in a noncompetitive manner (KI=4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ionophore: two regulatory components which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin. The dissociation constant for scorpion toxin binding is increased 10-fold by depolarization of the cells with K+, suggesting that the scorpion toxin binding site is located on a voltage-sensitive regulatory component of the ionophore.
 ...
PMID:Interactions of neurotoxins with the action potential NA + ionophore. 102 23

Four neurotoxins that activate the action potential Na+ ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin is a noncompetitive inhibitor of activation by each of these toxins (KI = 4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ ionophore: two regulatroy components, which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin.
 ...
PMID:Cooperative activation of action potential Na+ ionophore by neurotoxins. 105 69

Certain antiepileptic drugs are known to block sodium and calcium channels of excitable membranes. These channels are responsible for generation of action potentials. Various natural toxins, chemicals, and therapeutic drugs have been found to modify the gating kinetics of the sodium and/or calcium channels, thereby altering the excitation. Studies of such chemical modulations of the sodium and calcium channel gating provide the basis for understanding the mechanisms underlying epilepsies and the actions of antiepileptic drugs. Tetrodotoxin blocks the sodium channels, whereas batrachotoxin (BTX), grayanotoxin (GTX), and pyrethroids modify a population of the sodium channels to give rise to an extremely slow opening and/or closing. Patch-clamp techniques developed during the past few years permit measurements of opening and closing of individual ionic channels. When a membrane patch isolated from a neuroblastoma cell is depolarized, square inward currents of about 1 pA in amplitude and 2 msec in duration are observed at 10 degrees C. After exposure of the membrane to BTX, the open time is prolonged, the single-current amplitude is reduced, and channel opening is observed at large negative potentials at which no opening is expected to occur in normal preparations. In the BTX-poisoned membrane, there are two separate groups of the sodium channels, one exhibiting the normal characteristics and the other exhibiting a prolonged opening and reduced amplitude. Tetramethrin also modifies the single sodium channel in a similar manner to BTX, but fails to affect the amplitude of single-channel current. Neuroblastoma cells are also endowed with calcium channels, which undergo inactivation in a manner dependent upon membrane potential.
 ...
PMID:Modulators acting on sodium and calcium channels: patch-clamp analysis. 242 92

When SK-N-SH human neuroblastoma cells were exposed to nicotine (NIC) or KCl they showed a dose-dependent transient increase (2- to 4-fold) in intracellular Ca2+ concentration ([Ca2+])i as detected by quin-2 fluorescence, with half maximal effects (EC50) observed at 13 microM and 26 mM, respectively. Tubocurarine and 1-isodihydrohistrionicotoxin potently blocked the NIC-evoked (IC50 congruent to 1 microM and 0.3 microM, respectively), but not the high [K+]o-evoked [Ca2+]i accumulation. The KCl-induced response was inhibited by verapamil and diltiazem (IC50 = 1.4 and 10.9 microM, respectively). Tetrodotoxin (3 microM) and tetraethylammonium (10 microM) had no effect on [Ca2+]i accumulation induced by either agent. Increases in [Ca2+]i could be evoked sequentially by NIC and KCl in the same cells suggesting independent mechanisms of Ca2+ entry. In a Ca2+-free medium, no response to either KCl or NIC was observed. However, when Ca2+ ions were restored, [Ca2+]i accumulation was enhanced to the same extent as cells suspended in a Ca2+-containing buffer. Long-term (18 hr) pretreatment of SK-N-SH cells with pertussis (100 ng/ml) or cholera toxins (10 nM) had no effect on NIC or KCl-induced [Ca2+]i accumulation. Together, these data demonstrate the presence of NIC receptors and voltage-sensitive Ca2+ channels on SK-N-SH neuroblastoma cells, through which [Ca2+]i may be modulated.
 ...
PMID:Calcium influx mediated by nicotinic receptors and voltage sensitive calcium channels in SK-N-SH human neuroblastoma cells. 254 92

The effects of tetrodotoxin on single Na+-channel currents recorded from excised patches of neuroblastoma cells were examined. Tetrodotoxin was found to cause a dose-dependent reduction in the frequency at which Na+ channels conduct during a series of depolarizations. Surviving conducting states had normal open times and current amplitudes. These effects could be explained by a model which includes initial binding of tetrodotoxin to a closed state of the channel with stable, complete block during the time the channel would normally be gated open.
 ...
PMID:All or none block of single Na+ channels by tetrodotoxin. 257 56

The regulation of cytoplasmic pH (pHi) was examined in neuroblastoma X glioma hybrid cell-line cells (NG108-15 cells) using 2,7-biscarboxyethyl-5(6)-carboxyfluorescein. The pHi of NG108-15 cells suspended in nominally HCO-3-free, Na+-containing buffer could be reduced by the external application of acetate. The recovery of pHi to its resting value was blocked by the removal of extracellular Na+, by the addition of extra-cellular H+, and by the addition of analogs of amiloride selective for inhibition of Na+/H+ exchange. The rate of recovery of pHi from acid load exhibited an ionic selectivity of Na+ greater than Li+ much greater than K+, and no recovery was observed in N-methyl-D-glucamine+. Tetrodotoxin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid had no effect on early pHi recovery. These data suggest that Na+/H+ exchange accounts primarily for the recovery of pHi in NG108-15 cells under our experimental conditions. Na+/H+ exchange in NG108-15 cells was accelerated by alpha 2-adrenergic receptors. Thus, (-)epinephrine, but not (+)epinephrine, elicited an intracellular alkalinization which was blocked by the alpha 2-adrenergic receptor selective antagonist yohimbine but not by the alpha 1-adrenergic receptor antagonist, prazosin, nor the beta-adrenergic antagonist, propranolol. Norepinephrine, clonidine, and the clonidine analog, UK-14304, also caused alkalinization of NG108-15 cells, whereas isoproterenol, a beta-adrenergic receptor agonist, and phenylephrine, a selective alpha 1-adrenergic receptor agonist, did not. Manipulations that blocked Na+/H+ exchange blocked the ability of alpha 2-adrenergic agonists to alkalinize the interior of NG108-15 cells without blocking the ability of these agonists to attenuate cAMP accumulation. These findings provide the first direct evidence of modulation of Na+/H+ exchange activity by a receptor linked to inhibition of adenylate cyclase and offer a possible mechanism whereby alpha 2-adrenergic receptors might influence cellular activity apart from changes in cyclic nucleotide metabolism.
 ...
PMID:Alpha 2-adrenergic receptors accelerate Na+/H+ exchange in neuroblastoma X glioma cells. 288 87

In the presence of ouabain, veratridine enhances sodium influx in the mouse neuroblastoma cell line Neuro-2A (ATCC, CCL131), causing cellular swelling and subsequent death. Tetrodotoxin (puffer fish toxin) or saxitoxin (paralytic shellfish poison), both of which block the sodium channel of excitable membranes, antagonize this effect, enabling cell growth to continue. This phenomenon was used as the basis of a new assay for these toxins. It is also possible to estimate the quantity of TTX from the relationship between TTX concentration and percentage of living cells. This new method is simple, inexpensive, and sensitive, and may replace the conventional mouse bioassay.
 ...
PMID:A tissue culture assay for tetrodotoxin, saxitoxin and related toxins. 336 66

The effects of highly purified toxin gamma from the venom of the scorpion Tityus serrulatus (TiTx gamma) on nerve membrane ionic channels have been investigated using the suction electrodes voltage clamp technique on neuroblastoma cells. The amplitude of the normally voltage-dependent Na current is reversible reduced by approximately 50% after 15-105 nM TiTx gamma, whereas even the highest toxin concentrations have no significant effect on the outward K current in the presence of tetrodotoxin. TiTx gamma causes a transient inward current to appear at membrane potentials between -70 and -40 mV, a potential region in which no significant inward current is observed in control experiments. Tetrodotoxin (300 nM) rapidly blocks both the TiTx gamma-induced inward current and the remaining normally voltage-dependent Na current. The binding of radiolabelled TiTx gamma to the Na channels in the neuroblastoma cell membrane is prevented by native TiTx gamma with a K0.5 = 0.75 nM. Both activation and inactivation of the TiTx gamma-induced Na current are shifted 30-40 mV towards more negative potential values as compared to normally voltage-dependent Na current. The TiTx gamma-induced Na current exhibits sigmoidal activation kinetics and relatively slow, exponential inactivation kinetics. The local anesthetic procaine at an external concentration of 1 mM blocks more effectively the remaining normally voltage-dependent Na current than the TiTx gamma-induced Na current. Both Na current components are equally blocked by 1 mM of the local anesthetic propoxycaine. The relation between the effects of TiTx gamma on Nat channels and those of other known neurotoxins those of other known neurotoxins specific of this channel is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of Tityus serrulatus scorpion toxin gamma on Na channels in neuroblastoma cells. 608 1

The properties of interactions of several polypeptide neurotoxins isolated from sea anemone and scorpion venom with Na+ channels of rat myoblasts, chick myotubes, neuroblastoma cells, and fibroblasts have been compared. Tetrodotoxin (TTX)-resistant Na+ channels appear to be much more sensitive to the action of sea anemone toxins than TTX-sensitive Na+ channels but have the same affinity for scorpion neurotoxins. This conclusion holds both for Na+ channels that can be activated electrically and for silent forms of Na+ channels. The sensitivity to sea anemone toxins of the different types of Na+ channels that have been studied suggests the existence of multiple forms of Na+ channels.
 ...
PMID:The interaction of sea anemone and scorpion neurotoxins with tetrodotoxin-resistant Na+ channels in rat myoblasts. A comparison with Na+ channels in other excitable and non-excitable cells. 614 26

A study was made of the Rb+ transport via activated sodium channels of clone N 18 phi 1 neuroblastoma cells cultured in the Eagle medium with 10% bovine serum. The time of population doubling was about 10 h. The cell differentiation was induced by adding bromdeoxyuridine in a concentration of 1-4 10(-5) M. The cells contained 172 +/- 12 and 340 +/- 35 micrograms of protein per 10(6) cells at the logarithmic growth phase and in differentiated state, respectively. It is shown that veratrin produced a 1.3-fold increase in the rate of 86Rb+ removal from undifferentiated cells and 2.5-fold increase in that from differentiated cells. Tetrodotoxin removed completely the effect of veratrin. A conclusion is made on the presence of a new clone of fast sodium channels in cell membranes.
 ...
PMID:[Transport of Rb+ via activated sodium channels of clone N 18 phi 1 neuroblastoma cells]. 631 14


1 2 Next >>