UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

External application of bradykinin to neuroblastoma X glioma hybrid NG108-15 cells produced a sustained depolarization preceded by a transient hyperpolarization. Bradykinin also increased the frequency of miniature end-plate potentials recorded from cultured striated muscle cells which had been innervated by NG108-15 cells. Parallelism between facilitative phases of miniature end-plate potentials and depolarization indicates that bradykinin caused an enhanced synaptic transmission from NG108-15 cells due to depolarization. Effects of bradykinin on phospholipid metabolism in the hybrid cells were then examined to shed light upon the mechanism by which bradykinin-receptor interaction leads to facilitation of synaptic transmission. Bradykinin induced specific incorporation of 32Pi into phosphatidic acid and phosphatidylinositol without affecting [3H]glycerol incorporation into these phospholipids by 10 min after its addition. The addition of bradykinin to hybrid cells prelabeled with 32Pi caused a transient decrease (maximal effect seen at 10-30 s) in the radioactivity from phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) which was followed by the accumulation of radioactivity in phosphatidic acid and phosphatidylinositol. A Ca2+ ionophore, A23187, failed to induce the initial degradation of PI-4,5-P2. The data show that the magnitudes of bradykinin-induced PI-4,5-P2 degradation and membrane potential changes in NG108-15 cells are both dependent on the concentration of bradykinin and that the degradation of PI-4,5-P2 precedes the electrophysiological responses. Taken together with the finding that bradykinin induced a transient increase in Ca2+ influx (at 10-20 s), it appears that a rapid and transient degradation of PI-4,5-P2 might be related to the initiation of the NG108-15 cell activities through mobilization of extracellular Ca2+ into the cells.
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PMID:Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells. 608 87

Cells of the murine neuroblastoma clone N1E-115 possess muscarinic receptors that influence the intracellular level of cyclic nucleotides. The stimulation of [3H]cyclic GMP levels occurs only with intact cells and has an EC50 near the "low-affinity" agonist equilibrium dissociation constant (KL) determined by radioligand binding assays. The inhibition of prostaglandin E1-stimulated [3H]cyclic AMP formation has an EC50 close to the value for the "high-affinity" agonist equilibrium dissociation constant (KH). During sequential subculturing in medium supplemented with newborn bovine serum, the inhibition of [3H]cyclic AMP was maintained, but the [3H]cyclic GMP response declined dramatically, and after 7 subculturings it was essentially absent. The time course for [3H]cyclic GMP formation in a late subculture with an 88% loss of the response was identical with the time course in early subcultures. A normal [3H]cyclic GMP response to bradykinin and histamine was demonstrated to be present in cells that had lost the [3H]cyclic GMP response to carbachol. The EC50 and KD values for the two muscarinic responses and binding sites increased 3- to 4-fold after several subculturings. A 90% loss of low-affinity binding sites was closely correlated with a similar loss of the [3H]cyclic GMP response. High-affinity binding sites did not decline significantly in concentration until the 11th subculture, where the total number of muscarinic sites was only 6% of the earliest subculture. In all subcultures, however, the ability of the muscarinic receptor to decrease [3H]cyclic AMP levels was maintained. These data, which show that the subculturing of N1E-115 cells in medium supplemented with newborn calf serum results in a selective loss of one muscarinic function, strongly support the hypothesis that these cells contain two separate muscarinic receptor-effector systems. One receptor subtype or conformation has a low affinity for the agonist and mediates cyclic GMP formation. The other receptor subtype or conformation has a higher affinity for the agonist and mediates an inhibition of prostaglandin E1-stimulated cyclic AMP formation.
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PMID:Muscarinic responses and binding in a murine neuroblastoma clone (N1E-115). Selective loss with subculturing of the low-affinity agonist site mediating cyclic GMP formation. 614 90

A clone of murine neuroblastoma (N1E-115) was shown to have functional receptors for the nonapeptide bradykinin. These receptors mediated a large, rapid (about 1 min to peak) and calcium-dependent increase in cyclic GMP. The median effective concentration (EC50) averaged 1.4 nM. In addition, this event was inhibited by quinacrine, 5,8,11,14-eicosatetraynoic acid, and nordi-hydroguaiaretic acid, suggesting involvement of phospholipase A2 with subsequent formation of lipoxygenase metabolities of arachidonic acid. [3H]Bradykinin binding to intact cells, investigated under conditions nearly identical to those used in the cyclic GMP assay, yielded binding sites with KDS of 0.83 pM, 1.0 nM, and 4.9 nM with respective Bmax values of 12, 160, and 250 fmol/10(6) cells. Apparently, the cyclic GMP response was associated with the binding site in which the KD = 1.0 nM. Peptide analogs of bradykinin stimulated cyclic GMP with EC50S nearly identical to their respective KDS determined in binding assays with [3H]bradykinin, thus providing evidence for receptor specificity of this response. This finding of a biochemical response of bradykinin promises to make N1E-115 cells a convenient model system for study of neuronal bradykinin receptors.
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PMID:Bradykinin receptor-mediated cyclic GMP formation in a nerve cell population (murine neuroblastoma clone N1E-115). 614 70

Substance P stimulated the uptake of guanidinium in neuroblastoma X glioma hybrid cells and neuroblastoma cells but not in polyploid glioma cells. Guanidinium has previously been shown to pass the action potential Na+ channel in the two neuronal cell lines. Half-maximal stimulation was reached at 3 microM substance P and, with the hybrid cells, a saturation was seen above 10 microM. The analogue (D-Pro2,D-Trp7,9)-substance P, recently described as a substance P antagonist, caused a stimulation of guanidinium uptake comparable to that seen in the presence of substance P and did not inhibit the stimulation exerted by substance P. The pharmacological properties of the substance P-activated ion channel were investigated. Tubocurarine, phentolamine and propranolol blocked the substance P-stimulated guanidinium uptake with half-maximal inhibitory concentrations of 0.5, 5 and 50 microM. A similar characteristics has been found previously with the veratridine-activated Na+ channel in the cell lines investigated here. Peptides structurally related to substance P such as physalaemin and eledoisin, or others such as neurotensin, bradykinin, D-Ala2, Met5-enkephalinamide and ACTH(1-24) did not affect guanidinium uptake. In view of the high concentrations of substance P required for eliciting an effect in the cell lines, the involvement of specific receptors is questioned. A direct interaction of the peptide with the action potential Na+ channel is discussed.
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PMID:Substance P enhances cation permeability of neuronal cell lines. 618 89

Veratridine induces membrane potential oscillations in non-excitable glioma cells, which are not affected by ouabain (2 mM) or by D600 (0.1 mM). In the presence of veratridine, scorpion toxin causes depolarization of the glioma cells to a positive value of the membrane potential. These effects of veratridine and of scorpion toxin are observed in Na+ but not in choline medium and are inhibited by tetrodotoxin. The response of the glioma cells to bradykinin has also been studied during these experiments. Previously bradykinin has been shown in these cells to induce a hyperpolarizing response caused by an increase in K+ conductance. This response to bradykinin can still be seen during the veratridine-induced oscillations of the membrane potential. In the glioma cells the uptake of guanidinium, a substitute for Na+, is enhanced by veratridine plus scorpion toxin. This stimulation is tetrodotoxin-sensitive. However, in the excitable neuroblastoma X glioma hybrid cells studied for comparison, veratridine causes membrane potential oscillations accompanied at the rising phase by one action potential or a train of action potentials. The results demonstrate that in non-excitable glioma cells tetrodotoxin-sensitive Na+ channels can be activated by veratridine and by scorpion toxin.
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PMID:Sodium-channels in non-excitable glioma cells, shown by the influence of veratridine, scorpion toxin, and tetrodotoxin on membrane potential and on ion transport. 631 Apr 81

The nonapeptide, bradykinin, elevated the level of cyclic GMP in two neural cell lines, neuroblastoma X glioma hybrid cells (clone 108CC15) and glioma cells (clone C6-4-2). In the hybrid cells the half-maximal stimulation occurred at 0.1 nM and the maximum was reached at 10 nM bradykinin. As soon as 30 s after the addition of bradykinin to the cultured cells, the intracellular concentration of cyclic GMP had increased maximally. The subsequent decline to the original level proceeded more slowly and lasted around 10 min. Hybrid cells incubated for 10 min in the presence of bradykinin and washed thereafter, did not respond at all to a subsequent 1 min challenge incubation with bradykinin. This nearly complete desensitization lasted for a period of 20 min. One hour after removal of bradykinin the original response to the peptide was restored. Modified and partial sequences of bradykinin were also investigated for their ability to induce the cyclic GMP response in the hybrid cells. Removal of amino acids from either terminus of bradykinin led to an almost complete loss of activity. The data are discussed with respect to our previous observation that bradykinin causes a slow hyperpolarization response in these cell lines and that on prolonged exposure to the peptide the membrane potential response of the cells is lost due to desensitization.
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PMID:Bradykinin regulates the level of guanosine 3',5'-cyclic monophosphate (cyclic GMP) in neural cell lines. 631 12

Receptor binding of [3H]neurotensin was examined on membrane preparations derived from neuroblastoma X glioma NG108-15 hybrid cells. The specific binding was saturable and reversible, and a dissociation constant (Kd) was calculated to be about 0.24 nM from the rate constants. Scatchard analysis of neurotensin binding at equilibrium revealed a single class of binding sites with a Kd of 0.86 nM and a maximal binding capacity (Bmax) of 250 fmol/mg of protein (7700 receptor sites/cell). [D-Arg9]-Neurotensin had a high affinity (IC50 = 0.5 nM) for the neurotensin receptors, but [D-Phe11]-neurotensin had a lower affinity (IC50 = 280 nM), while angiotensin II and bradykinin had almost no affinity for [3H]neurotensin-binding sites. Under similar conditions [3H]neurotensin binding to mouse and rat brain synaptosomal fractions showed two binding sites with high (0.86 and 0.44 nM) and low (13 and 19 nM) affinities. We have examined several possible physiological consequences of neurotensin receptor binding. Neurotensin (10 microM) exhibited no influence on adenylate cyclase activity, 45Ca uptake, or 32Pi incorporation into phosphatidylinositol fractions of NG108-15 cells. Electrophysiological study of isolated NG108-15 cells revealed neurotensin-induced transient hyperpolarization followed by sustained depolarization with enhanced membrane excitability. Application of neurotensin to NG108-15 cells that had formed synapses with cultured striated muscle cells caused a considerable increase in frequency of miniature endplate potentials from the muscle cells. These data show that NG108-15 cells possess a single class of neurotensin receptors similar to a high affinity site of synaptosomal membranes from the murine brains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A single class of neurotensin receptors with high affinity in neuroblastoma X glioma NG108-15 hybrid cells that mediate facilitation of synaptic transmission. 632 39

The effect of the nonapeptide bradykinin on the membrane potential of permanent cell lines from neural origin was studied. A hyperpolarizing response of 10-30 s duration was produced when bradykinin was iontophoretically applied onto polyploid rat glioma cells (clone C6-4-2). Starting from the resting membrane potential the peak value of the hyperpolarizing response was reached within 0.5-1.5 s. Then the potential returned more slowly to the original value. The hyperpolarization was associated with an approximately 50% decrease in membrane resistance. Neither Na+ nor Cl- seemed to be important for the hyperpolarizing response, since bradykinin elicited similar hyperpolarizations in cells exposed to media in which Na+ or Cl- were replaced by choline or isethionate, respectively. Ca2+ fluxes are unlikely to be involved, since the addition of D600 did not affect the hyperpolarizations induced by bradykinin. However, a 10-fold increase in the concentration of K+ in the medium reduced the amplitude of the hyperpolarization by 40 mV. Thus, the hyperpolarization induced by bradykinin is associated with decrease in membrane resistance which is likely to be caused by an increased K+-conductance. The glioma cells showed a desensitization upon repeated application of bradykinin. However, the sensitivity of the cells to bradykinin was restored after 3-8 min of incubation in the absence of bradykinin. Since an antagonist of bradykinin is not known, the specificity of the action of bradykinin is difficult to assess. Nevertheless, the hyperpolarizing response to bradykinin appears to be specific insofar as other peptides, i.e. lutoliberin, thyroliberin, neurotensin, substance P and apamin, exerted no effect on the membrane potential of the glioma cells. Bradykinin-elicited hyperpolarizations with characteristics similar to those described above could also be demonstrated in neuroblastoma X glioma hybrid cells, but not in multinucleated fibroblast cells.
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PMID:Bradykinin induces hyperpolarizations in rat glioma cells and in neuroblastoma X glioma hybrid cells. 709 75

The Ca indicator fura 2 was used to study the modulation of cytoplasmic Ca by bradykinin (Bk) in single N1E-115 murine neuroblastoma cells. Increases in cytoplasmic Ca in response to Bk were mediated by the B2 receptor subtype. Responses to high concentrations of Bk (1-100 nM) were homogeneous and characterized by a rapidly rising transient that decayed to baseline in the continued presence of agonist, with a half-time of 15 s. Responses to low concentrations of Bk (100-500 pM) were more heterogeneous, with longer latencies and often with oscillations. Pretreatment with thapsigargin for 20 min prevented the Ca response, showing that the Ca change results from intracellular Ca release. Removal of external Ca had little effect on the response to Bk, indicating that the agonist does not activate Ca influx. The extent of Ca release and refilling after Bk was tested with ionomycin. A saturating dose of Bk (20 nM) mobilizes > 90% of stored Ca within 30 s, and this is replaced slowly. Replacement of external Na by N-methyl-D-glucamine to block Na/Ca exchange affected the Ca response, causing decreases in latency and in the period of Ca oscillations and increases in overall duration and peak amplitude of the response.
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PMID:Intracellular calcium signals in response to bradykinin in individual neuroblastoma cells. 748 51

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