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

The mechanism underlying the bradykinin (BK)-induced increase of acetylcholine (ACh) release was studied in neuroblastoma x glioma hybrid NG108-15 cells and their synapses formed onto mouse muscle cells. External application of BK or iontophoretic injection of extrinsic inositol 1,4,5-trisphosphate (InsP3) into the cytoplasm of NG108-15 cells produced membrane hyperpolarization in the hybrid cells and an increase in the frequency of miniature end-plate potentials (MEPPs) in paired myotubes. Ba2+ blocked the hyperpolarization in response to BK, but facilitation of MEPPs was still observed. InsP3-dependent facilitation of MEPPs was also observed in cells where the InsP3 injections produced no detectable hyperpolarization or even depolarization. Real-time quantitative monitoring of intracellular free Ca2+ concentration [( Ca2+]i) with fura-2 in single NG108-15 cells showed that BK application or InsP3 injection induced an elevation of [Ca2+]i which coincided in time with membrane hyperpolarization recorded from the same cell. The [Ca2+]i rise produced by InsP3 injection started from the single site of injection and that produced by BK began from a deep compartment of the cytoplasm of the NG108-15 cells. The BK- and InsP3-evoked facilitation of MEPPs and the [Ca2+]i rise were relatively independent of extracellular Ca2+. These findings suggest that the BK-induced ACh release results not from membrane potential changes but from a transient InsP3-dependent elevation of [Ca2+]i.
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PMID:Bradykinin-evoked acetylcholine release via inositol trisphosphate-dependent elevation in free calcium in neuroblastoma x glioma hybrid NG108-15 cells. 230 64

Hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) produces two prospective intracellular messengers: inositol 1,4,5-trisphosphate (InsP3), which releases Ca2+ from intracellular stores; and diacylglycerol (DG), which activates protein kinase C. Here we show how the formation of these two substances triggered by one external messenger, bradykinin, leads to the appearance of two different sequential membrane conductance changes in the neurone-like NG108-15 neuroblastoma-glioma hybrid cell line. In these cells bradykinin rapidly hydrolyses PtdIns(4,5)P2 to InsP3 and DG, raises intracellular Ca2+ and hyperpolarizes then depolarizes the cell membrane. By voltage-clamp recording we show that the hyperpolarization results from the activation pharmacologically-identifiable species of Ca2+-dependent K+ current. This is also activated by intracellular injections of Ca2+ or InsP3 so may be attributed to the formation and action of InsP3. The subsequent depolarization results primarily from the inhibition of a different, voltage-dependent K+ current, the M-current that is also inhibited by DG activators. Hence we describe for the first time a dual, time-dependent role for these two intracellular messengers in the control of neuronal signalling by a peptide.
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PMID:Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. 242 90

Application of bradykinin to voltage-clamped N1E-115 mouse neuroblastoma cells evoked sequential outward and inward membrane currents, accompanied by an increase and decrease of membrane conductance, respectively. Methacholine produced an inward current with a decreased conductance. The outward current response to bradykinin was imitated by intracellular inositol 1,4,5-trisphosphate (IP3). Bath application of phorbol dibutyrate induced an inward current and potentiated the response to IP3. We conclude that the response of these cells to bradykinin is identical to that of NG108-15 hybrid cells, and therefore may be attributed to the dual effects of inositol trisphosphate and diacylglycerol formed by hydrolysis of phosphatidylinositide.
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PMID:Bradykinin inhibits potassium (M) currents in N1E-115 neuroblastoma cells. Responses resemble those in NG108-15 neuroblastoma x glioma hybrid cells. 244 Jul 28

The effect of bradykinin on membrane potential, level of cyclic nucleotides and of cytosolic Ca2+-activity was determined in neural cell lines. Bradykinin induced a transient hyperpolarization followed by a depolarization in mouse neuroblastoma x rat glioma hybrid cells and in polyploid rat glioma cells. The reversal potential of the hyperpolarizing response depended on the extracellular K+ concentration. The K+ channel blockers, Ba2+, quinidine, and 4-aminopyridine, inhibited the response to bradykinin. This suggests that the hyperpolarization of ca. 1 min duration, which was accompanied by a decreased input resistance, is due to activation of K+ channels. Upon addition of bradykinin to the cells the cytosolic Ca2+-activity increased transiently. Ca2+ was involved in the induction of the hyperpolarization by bradykinin, since both removal of extracellular Ca2+ and injection of EGTA into the cells suppressed the membrane potential response. Bradykinin induced the formation of inositol-1,4,5-trisphosphate (IP3), an agent known to release Ca2+ from intracellular stores, and stimulated the uptake of 45Ca2+ into the cells. Therefore the increased level of intracellular Ca2+ activating the K+ conductance could be due to two components: release from intracellular pools and uptake. IP3 seems to be involved in the membrane potential response, because intracellular injection of either IP3 or Ca2+ into the glioma cells elicited a hyperpolarizing response which resembled that after application of bradykinin and was also susceptible to the K+ channel blocking agents listed above. However, the formation of cyclic GMP by bradykinin apparently plays no role in the membrane potential effect of bradykinin.
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PMID:The regulatory influence of bradykinin and inositol-1,4,5-trisphosphate on the membrane potential in neural cell lines. 244

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

In neuroblastoma x glioma hybrid cells (NG 108-15) labelled with [32P]-trisodium phosphate, [3H]-inositol and [14C]-arachidonic acid, bradykinin stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) while it had no effect on the release of [14C]-arachidonic acid (AA). The effect on PIP2 was time- and dose-dependent with a maximal effect on [3H]-inositol- and [32P]-labelled cells after 10-30 s of stimulation with 10(-6) M bradykinin. However, the hydrolysis of [14C]-AA labelled PIP2 was delayed compared to the effect on [3H]- and [14C]-PIP2 and was not detectable until after 60 s of stimulation. Bradykinin stimulation resulted in an increased formation of [3H]-inositol phosphates (IP) and [32P]- and [14C]-phosphatidic acid (PA) but the time course for PA formation did not follow the time-course for PIP2 hydrolysis. A reduced labelling of [32P]- and [14C]-phosphatidylcholine was also found in stimulated cells suggesting that PA may derive from other sources than PIP2. In conclusion, our results indicate that bradykinin activates phospholipase C, but not phospholipase A2, in NG 108-15 cells.
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PMID:Bradykinin effects on phospholipid metabolism and its relation to arachidonic acid turnover in neuroblastoma x glioma hybrid cells (NG 108-15). 251 58

Insulin and various growth factors (epidermal growth factor (EGF), insulin-like growth factor, fibroblast growth factor, and transforming growth factor alpha), which fail to modify the resting [Ca2+]i in PC12 rat pheochromocytoma and SKNBE human neuroblastoma cells when administered alone, became capable of inducing [Ca2+]i increases when administered a few (4-20) min after another agent, bradykinin. The latter peptide, working through a B2 receptor, caused hydrolysis of polyphosphoinositides and a large, biphasic [Ca2+]i transient (an initial (1-2 min) spike, originated primarily from intracellular stores, followed by a steady-state elevation dependent on Ca2+ influx). Priming by bradykinin of the growth factor effects was quickly dissipated by the addition of a B2 blocker. Activation of other receptors coupled to polyphosphoinositide hydrolysis: muscarinic and purinergic (in PC12 and SKNBE cells); bombesin and vasopressin receptors (in Swiss 3T3 cells), was without effect in priming. Bradykinin-primed, growth factor-induced [Ca2+]i rises in PC12 cells appeared after a 20-30-s delay; they were relatively small, but persistent; their concentration dependence was similar to that of other effects of the factors; and they included both release of Ca2+ from intracellular stores and stimulation of Ca2+ influx, preceded (in PC12 cells) by a transient increase of polyphosphoinositide hydrolysis. Thus the effect of growth factors (possibly dependent on the tyrosine kinase activity of their receptors) consisted in the reinforcement of the transmembrane signaling at B2 receptors. This is the first direct demonstration of a [Ca2+]i rise induced by insulin and insulin-like growth factor-I, and of such an effect of EGF in cell types endowed with a small number of specific EGF receptors.
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PMID:Reinforcement of signal generation at B2 bradykinin receptors by insulin, epidermal growth factors, and other growth factors. 253 35

Cd2+ and other divalent metals mobilized cell Ca2+ in human skin fibroblasts. The divalent metals produced a large spike in cytosolic free Ca2+ and strikingly increased net Ca2+ efflux similarly to bradykinin. One-tenth microM Cd2+ half-maximally increased 45Ca2+ efflux. The potency order of the Ca2+ mobilizing metals was: Cd2+ greater than Co2+ greater than Ni2+ greater than Fe2+ greater than Mn2+. Cd2+ probably acts at an extracellular site because loading the cells with a heavy metal chelator only slightly inhibited Cd2+-evoked 45Ca2+ efflux. Cd2+ increased [3H]inositol polyphosphates; [3H]inositol trisphosphate increased 4-fold in 15 s. Zn2+ reversibly blocked 45Ca2+ efflux evoked by Cd2+ but not that produced by bradykinin. Zn2+ competitively (Ki = approximately 0.4 microM) inhibited net Ca2+ efflux produced by Cd2+. Cd2+ also evoked Ca2+ mobilization in umbilical artery muscle, endothelial, and neuroblastoma cells, and the divalent cation agonist and antagonist specificities were similar to those in the fibroblasts. The divalent metals appear to trigger Ca2+ mobilization via a reversible interaction with an external site on the cell surface, which may be considered a "Cd2+ receptor."
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PMID:Cadmium evokes inositol polyphosphate formation and calcium mobilization. Evidence for a cell surface receptor that cadmium stimulates and zinc antagonizes. 254 Jan 74

The peptides bradykinin and kallidin are released in response to noxious stimuli and mediate various physiological effects, including a direct stimulation of nociceptive afferent neurones. The nature of the receptor molecules through which these ligands act is presently unknown. We synthesised an iodinatable photoaffinity probe, N epsilon-4-azidosalicylylkallidin, and used it in an attempt to identify candidate bradykinin receptors on the NG108-15 neuroblastoma X glioma hybrid cell line. The ligand bound in subdued light to a particulate fraction of NG108-15 tumours and could be displaced by bradykinin with an IC50 of 0.33 nM. In a physiological assay, it behaved as an agonist equipotent with bradykinin. Gel analysis of the labelled products after photolysis of the iodinated ligand in the presence of NG108-15 cells or tumour membranes revealed bradykinin-blockable labelling of a glycoprotein with an Mr of 166,000. The probe was also able to label purified commercial angiotensin converting enzyme. The band labelled in NG108-15 cells was immunoprecipitable with a polyclonal antiserum to angiotensin converting enzyme, an enzyme shown to be present in low amounts in these preparations by direct binding using the iodinatable specific ligand MK351A.
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PMID:Construction of a physiologically active photoaffinity probe based on the structure of bradykinin: labelling of angiotensin converting enzyme but not candidate bradykinin receptors on NG108-15 cells. 254 Feb 73

Here we report that the mouse neuroblastoma-glioma hybrid cell line NG108-15 possess high-affinity binding sites for the nonapeptide bradykinin, as revealed by competitive displacement of 125I-8Tyr bradykinin by various bradykinin analogs. These binding sites were further characterized by covalent cross-linking of 125I-8Tyr bradykinin to intact NG108-15 grown as a monolayer, using dithiobis-succinimidylpropionate (DTSP) as a cross-linking reagent. Sodium dodecyl sulfate (SDS) electrophoresis after solubilization of the cross-linked cells, demonstrated the preferential and specific labeling of two polypeptides with apparent molecular weights of Mr = 36,000 and Mr = 47,000. A third polypeptide of Mr = 69,000 was labeled less intensely.
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PMID:Molecular characteristics and peptide specificity of bradykinin binding sites in intact neuroblastoma-glioma cells in culture (NG 108-15). 255 Aug 44


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