Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of 3 cases of hypothalamic tumours (glioma of the hypothalamus or of the stem of the pituitary, glioma of the hypothalamus or of the optic chiasma, pinealoblastoma), the authors emphasise: (1) the existence of a special endocrine "formula" since it often combines anterior pituitary insufficiency, diabetes insipidus and moderate hyperprolactinaemia; (2) the remarkable efficacy, in all 3 cases, of cobalt therapy, tumour regression becoming complete during the 6 to 10 months following the end of radiotherapy; (3) the post-radiotherapeutic endocrine complications, endocrine deficit becoming greater whilst the tumour disappeared; (4) the diagnostic possibilities and above all regular surveillance now made possible by tomodensitometry.
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PMID:[Three hypothalamic tumours: clinical, biologic, X-ray and therapeutic study (author's transl)]. 51 17

The characteristics of 5'-nucleotidase in a clonal line (C6) of rat glioma cells has been examined in detail. The cells liberated 6.80 +/- 0.33 mumol of inorganic phosphate/mg of cell protein/hour, producing nearly equimolar amounts of adenosine and inorganic phosphate from AMP in the extracellular fluid. No 5'-nucleotidase was released by the cells into the medium. Most of the 5'-nucleotidase activity was found to be located in the outer surface of the plasma membrane of C6 cells and rapidly accessible to exogenous AMP, by experiments based upon differential labeling of extracellular and intracellular compartments with 32P and 33P. The ecto-enzyme was active in the absence of divalent cations. However, Mn2+ or Co2+ were somewhat stimulatory. Zn2+ suppressed activity very markedly. The relationship of enzymatic reaction velocity to pH was complex, with an optimum at pH 7.4 for all substrates tested. The ecto-5'-nucleotidase readily hydrolyzed 5'-AMP and 5'-UMP. Other 5'-nucleoside monophosphates, including 5'-deoxy-AMP, were also hydrolyzed, but more slowly; 2'- or 3'-nucleoside monophosphates were not attacked. The ecto-5'-nucleotidase in the intact cell obeyed Michaelis-Menten kinetics. Apparent Km for AMP was 0.22 mM; apparent Km values for other substrates were similar and ranged from 0.16 to 0.18 mM. ADP exerted a very powerful inhibitory effect, behaving as a competitive inhibitor, and 5'-UMP behaved as a strictly competitive substrate for 5'-AMP. ATP and ITP were inhibitory. Of these, ITP served to increase Km for AMP. ATP did likewise, but also greatly lowered Vmax. These findings indicate that the intact cell is capable of rapid hydrolysis of exogenous 5'-AMP, to produce adenosine at the cell surface at a rate which responds directly to extracellular AMP concentration but which can be suppressed by extracellular ADP or ATP.
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PMID:Ecto-5'-nucleotidase of intact cultured C6 rat glioma cells. 81 33

Electrical excitability is one of the various neuronal properties of neuroblastoma X glioma hybrid cells. At a Ca2+ concentration of 1.8 mM the action potential is inhibited by tetrodotoxin, suggesting that the inward current is carried by Na+ ions. In contrast, at a Ca2+ concentration of 20-36 mM and even in the absence of Na+, spikes (sometimes repetitive) with strong hyperpolarizing afterpotential occur, which are no longer affected by tetrodotoxin. They are, however, blocked by antagonists of Ca2+ like La3+, Co2+, Mn2+, and the synthetic compounds D-600 and BAY a-1040. This seems to indicate that at high concentrations of Ca2+, the inward current of the action potential is essentially carried by Ca2+. Sr2+, but not Mg2+ can effectively substitute for Ca2+. It slows down the time course of the action potential. Ba2+ depolarizes the membrane gradually. If Ca2+ is also present, Ba2+ causes a reduced depolarization and spontaneous action potentials with no hyperpolarizing after-potential are observed.
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PMID:Influence of cations on the electrical activity of neuroblastoma X glioma hybrid cells. 89 Apr 47

Maitotoxin elicits a dose-dependent stimulation of 45Ca2+ influx in glioma C6, pheochromocytoma PC12, insulinoma HIT and human blood cells, while having no effect in liposomes. In HIT cells maitotoxin also elicited influx of 86Rb+ greater than 22Na+ greater than 54Mn2+, but the stimulation was far less than for 45Ca2+. Stimulation of 45Ca2+ influx was blocked by Ni2+, Co2+, Cd2+ and Mn2+, and markedly reduced by Ba2+. Divalent cations, in particular Ca2+, Ba2+, Mn2+ and Cd2+, enhanced influx of the monovalent cations 22Na+ and 86Rb+.
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PMID:Selective stimulation of Ca2+ flux in cells by maitotoxin. 133 Jun 38

1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino-1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. 140 9

1. The whole-cell patch-clamp technique was used to examine the effects of the class III antidysrhythmic agent, clofilium, on voltage-activated delayed rectifier K+ currents (IKv) in undifferentiated mouse neuroblastoma x rat glioma hybrid (NG 108-15) cells. Ca(2+)-activated K+ currents also seen in these cells were abolished by bath application of 4 mM Co2+. 2. Bath application of clofilium (0.3 to 70 microM) caused dose-dependent, irreversible inhibition of IKv in these cells. Under control conditions, activated currents were sustained during 200 ms depolarizing steps, but in the presence of clofilium, or after its wash-out, currents were reduced in amplitude and showed a time-dependent decay. 3. Clofilium blockade of IKv was voltage-dependent; the degree of current inhibition increased with increasing depolarizations. The transient nature of IKv seen in the presence of clofilium was also more apparent at higher test potentials. 4. The effects of clofilium were use-dependent: when cells were left unstimulated during drug application, and then depolarizations were resumed, several pulses were required for clofilium blockade to reach a steady level. Similar results were obtained post-clofilium, when cells were unstimulated during application and then removal of clofilium, suggesting that although the blocking action of the drug was use-dependent, it bound to the closed, delayed rectifier K+ channel. 5. High concentrations (100 or 300 microM) of sotalol, another class III antidysrhythmic agent, were without discernible effects on IKv in NG 108-15 cells. 6. The effects of clofilium on a neuronal IKv described here, and its possible mechanism of action, are compared with previously reported effects of clofilium on the cardiac IKv.
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PMID:Blockade of delayed rectifier K+ currents in neuroblastoma x glioma hybrid (NG 108-15) cells by clofilium, a class III antidysrhythmic agent. 155 35

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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PMID:Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. 179 58

Extracellular application of bradykinin and injection of inositol-1,4,5-trisphosphate (Ins-P3) induced a hyperpolarization in polyploid rat glioma cells. Ins-1,4,5-P3 and Ins-2,4,5-P3 were effective but not Ins-4,5-P2, Ins-1,3,4,5-P4 and Ins-1,3,4,5,6-P5. The reversal potential of the hyperpolarizing response induced by bradykinin or by Ins-P3 increased to a comparable degree with increasing the extracellular K+ concentration. Certain blockers of K+ channels, for example charybdotoxin (5-50 nM), Ba2+ (5-20 mM), 4-aminopyridine (5-10 mM) and quinidine (0.1-0.5 mM) reversibly suppressed the membrane potential response to bradykinin or to Ins-P3; however, apamin (1 microM) and D-tubocurarine (0.5 mM) had no effect. Intracellular injection of EGTA made the glioma cells unresponsive to bradykinin. Superfusion of the cells with Ca2(+)-free medium gradually and reversibly abolished the response to bradykinin, but only slightly reduced the effect of Ins-P3. The Ca2+ channel blockers Co2+ (1-5 mM), Mn2+ (2-6 mM) and nifedipine (1-20 microM), but not desmethoxyverapamil (100 microM) inhibited the hyperpolarizing effect of bradykinin. The hyperpolarization induced by Ins-P3, however, was not influenced by Mn2+ (1-5 mM) or by Co2+ (7 mM). Injection of Ca2+ into the glioma cells induced a hyperpolarization susceptible to Ba2+ and quinidine. Treatment of glioma cells with an activator or with inhibitors of protein kinase C or with pertussis toxin did not affect the response to bradykinin. Incubation of the cells with the Ca2+ ionophore A23187 (0.1-1 microM) made the cells unresponsive to bradykinin and, somewhat less, to Ins-P3. At these concentrations the Ca2+ ionophore primarily depletes intracellular Ca2+ stores. In summary, bradykinin, via B2-receptors (blocked by [Thi5,8, D-Phe7]-bradykinin) activates a K+ conductance in glioma cells following a rise of cytosolic Ca2+ activity most likely due to Ins-P3-mediated release of Ca2+ from internal stores. Entry of extracellular Ca2+ appears also to be involved in this process.
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PMID:Activation of a K+ conductance by bradykinin and by inositol-1,4,5-trisphosphate in rat glioma cells: involvement of intracellular and extracellular Ca2+. 230 62

Outward currents were recorded from voltage-clamped NG108-15 mouse neuroblastoma X rat glioma hybrid cells, differentiated with prostaglandin E1. Depolarising voltage steps from -70 mV, evoked a transient outward current from a threshold of -30 mV. The outward current showed complete inactivation at potentials positive to -10 mV. Inactivation was removed by hyperpolarisation with half-inactivation at -53 mV. The time course of the inactivation could be best fitted by two exponentials with mean time constants of 280 ms and 1.6 s at +80 mV. Tail current measurements showed a shift in the reversal potential with changes in external K+ concentration, consistent with K+ as the current-carrying ion. The outward current amplitude was reversibly reduced by 4-aminopyridine, and the time course of inactivation modified. In the presence of other K+ channel blockers (tetraethylammonium, barium and tetrahydroaminoacridine) the amplitude of the outward current was also reversibly reduced, but with a negligible effect on its time course. The current was unaffected by dendrotoxin, d-tubocurarine, apamin, Cd2+ and Ni2+, and by replacing external Ca2+ with Co2+ or Mg2+. In current clamp, action potential duration was greatly increased by 4-aminopyridine. The findings show that the NG108-15 cell line displays a transient outward current that resembles IK(A) but with a higher than usual threshold and relatively slow inactivation, and that this current is likely to be important for action potential repolarisation.
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PMID:A transient outward current in NG108-15 neuroblastoma x glioma hybrid cells. 235 30

1. Membrane current responses to focal application of bradykinin (BK) were recorded in voltage-clamped NG108-15 neuroblastoma x glioma hybrid cells. 2. BK produced sequential outward and inward currents at clamp potentials between -60 and -30 mV, designated IBK(out) and IBK(in), respectively. 3. The outward current IBK(out) was accompanied by an increased membrane conductance. Ramp current-voltage (I-V) curves yielded a reversal potential (VBK) of -80 +/- 5.6 mV (mean +/- S.D., n = 9) in 5.4 mM [K+]o. VBK showed a positive shift on raising [K+]o, compatible with a primary increase in K+ conductance. Subtracted I-V curves indicated that the underlying conductance was not strongly voltage dependent between -120 and -40 mV. 4. IBK(out) was inhibited by d-tubocurarine (dTC, 0.1-0.5 mM) but was insensitive to tetraethylammonium (TEA) below 5 mM. 5. The inward current IBK(in) was accompanied by a fall in membrane conductance. This was associated with the inhibition of a time- and voltage-dependent K+ current, IM. In consequence, IBK(in) was strongly voltage dependent and dissipated, usually without reversal, on hyperpolarizing the cell beyond -70 mV in 5.4 mM [K+]o. Reversal to an outward current negative to -40 mV could be obtained on raising [K+]o to 54 mM. 5. Both IBK(in) and IBK(out) persisted when ICa was blocked with Co2+ or Cd2+. IBK(out) slowly diminished in Ca2+-free, Mg2+-substituted solution. 6. The Ca2+ spike current ICa and the Ca2+-activated K+ current IAHP were inhibited during IBK(out) or after Ca2+ injections. BK did not affect the voltage-activated K+ current IK(V) recorded in Co2+ solution. 7. It is concluded that the dual response to BK results from opposing effects on two different species of K+ current. IBK(out) results from activation of a Ca2+-dependent, voltage-insensitive K+ conductance, probably mediated by a transient rise in intracellular Ca2+. It is suggested that the Ca2+ is released from an intracellular store. IBK(in) results primarily from inhibition of the Ca2+-independent, voltage-gated K+ current, IM. This effect is not replicated by a rise of intracellular Ca2+ and must therefore be generated by another mechanism.
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PMID:Membrane current responses of NG108-15 mouse neuroblastoma x rat glioma hybrid cells to bradykinin. 245 96


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