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)

Bradykinin (BK) induced a transient and pertussis toxin (PT)-insensitive increase in cytosolic Ca2+ ([Ca2+]i) in NG 108-15 neuroblastoma x glioma hybrid cells, whereas leucine-enkephalin (EK), somatostatin, norepinephrine or carbachol showed a weak but PT-sensitive action. When any one of the latter agonists was applied to the cells treated with low doses of BK, however, the level of [Ca2+]i rise caused by the agonist was remarkably increased in a PT-sensitive manner. The decreasing of extracellular Ca2+ only slightly influenced the actions of these agonists. Thus, synergism between a BK receptor and PT-sensitive G-protein-coupled receptors results in marked intracellular Ca2+ mobilization by the latter agonists.
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PMID:Synergism in cytosolic Ca2+ mobilization between bradykinin and agonists for pertussis toxin-sensitive G-protein-coupled receptors in NG 108-15 cells. 134 83

Long-term ethanol exposure is known to inhibit bradykinin-stimulated phosphoinositide hydrolysis in cultures of neuroblastoma x glioma 108-15 cells. In the present study, [3H]bradykinin binding, GTP-binding protein function, and phospholipase C activity were assayed in cells grown for 4 days in 100 mM ethanol with the aim of elucidating the molecular target of ethanol on signal transduction coupled to inositol trisphosphate and diacylglycerol formation. Ethanol exposure reduced guanosine 5'-O-(3-thiotriphosphate) [GTP(S)]- and, to a lesser extent, NaF/AlCl3-stimulated phosphoinositide hydrolysis, whereas it had no effect on the enzymatic activity of a phosphatidylinositol 4,5-bisphosphate-specific phospholipase C. [3H]Bradykinin binding in the absence of GTP(S) was not influenced by ethanol exposure. However, the reduction in [3H]bradykinin binding seen in control cells after addition of GTP analogue was inhibited in cells grown in ethanol-containing medium. The results indicate that long-term ethanol exposure exerts its effects on receptor-stimulated phosphoinositide hydrolysis primarily at the level of the GTP-binding protein.
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PMID:G proteins coupled to phospholipase C: molecular targets of long-term ethanol exposure. 185 Dec 10

Bradykinin triggered intracellular Ca mobilizations and ionic conductance changes were studied in the neuroblastoma x glioma hybrid cell line NG108-15 using Ca-sensitive fluorescent indicator fura-2 under patch pipette whole cell voltage clamp condition. The time course of outward current induced by bradykinin was closely related to the time-course of [Ca2+]i change. Following application of bradykinin, [Ca2+]i increased transiently and then decreased below the basal level before bradykinin application. The inward currents activated by step-depolarization were suppressed after bradykinin application, but the time-course of the suppression did not go in parallel with the [Ca2+]i changes: the suppression started before the [Ca2+]i change emerged and outlasted the phase of [Ca2+]i increase. Both transient type and long-lasting type Ca current were suppressed by bradykinin. [Ca2+]i increase induced by high potassium depolarization was suppressed by bradykinin. Pertussis toxin did not affect the Ca transient nor the suppression of Ca channel induced by bradykinin. Our results suggest that the modifications of ionic channels by bradykinin could be through the other mechanisms than the well established activation of the G-protein leading to the IP3 mechanisms and that the bradykinin receptor might couple with the pertussis toxin-insensitive G protein which regulates the calcium channels.
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PMID:Mobilization of intracellular Ca2+ and suppression of inward currents in a neuronal hybrid cell line triggered by bradykinin. 196 37

Secondary mediator compounds are postulated to have a role in vasogenic oedematogenesis. They may also cause focal brain dysfunction due to their neuronal, axonal and glial modulating properties. Using the feline model of infusion brain oedema the effects of right frontal intracerebral infusion (200 microliters/hr for 3 hrs) of saline, bradykinin (10(-4) to 10(-6) M), arachidonic acid (10(-2) to 10(-3) M), 20% protein and four human glioma cyst fluids were evaluated. Somatosensory evoked potentials (SSEP), motor evoked potentials (MEPs), rCBF and rCBF CO2 reactivity (Hydrogen clearance). ICP, craniospinal compliance, local brain tissue water content (microgravimety), brain histology and BBB function (Evans Blue 2%) were measured. Brain water content increased locally from 69% to 79%, ICP increased (by mean 14 mmHg) and compliance decreased (mean 70%) and there were the histological features of brain oedema with all infusates. BBB opening occurred with Bradykinin (+), arachidonic acid (++), 20% protein ( ) and glioma cyst fluid (4+). Polymorphic and macrophage infiltrates were seen with all infusions but rCBF and MEPs remained normal. SSEPs changed with high dose bradykinin and some glioma cyst infusates whilst CBF CO2 reactivity was locally impaired by all infusates except saline and arachidonic acid. This study suggests that certain compounds in brain oedema fluid could mediate local brain dysfunction.
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PMID:The contribution of secondary mediators to the etiology and pathophysiology of brain oedema: studies using a feline infusion oedema model. 212 86

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

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

Studies were undertaken to further elucidate the mechanism(s) by which bradykinin-dependent phosphoinositide metabolism takes place in neuroblastoma X glioma hybrid NG108-15 cells [(1984) J. Biol. Chem. 259, 10201-10207] using [3H]inositol-labelled cells. Bradykinin produced net increases in the level of [3H]inositol phosphates, especially of [3H]inositol trisphosphate which is formed transiently and most rapidly. The results indicate that bradykinin activates a phosphodiesterase to break down phosphatidylinositol 4,5-bisphosphate, generating two recently recognized intracellular messengers, 1,2-diacylglycerol and inositol trisphosphate.
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PMID:Bradykinin-induced transient accumulation of inositol trisphosphate in neuron-like cell line NG108-15 cells. 285 60

Bradykinin (BK) activation of phosphatidylinositide breakdown in NG108-15 neuroblastoma x glioma hybrid cells in the generation of an outward K+ current through the release of Ca2+ by the intermediary messenger inositol 1,4,5-trisphosphate (InsP3). Channels mediating this outward current were identified using cell-attached patch electrodes. Intracellular iontophoretic injection of InsP3 or Ca2+, or extracellular application of BK, evoked bursts of K+ channel activity coincident with cell hyperpolarization measured with an intracellular recording micropipette. The most frequent channels had a mean single-channel conductance of about 40 pS in symmetrical K+ solutions; additional openings of lower conductance (18 pS) channels were also detected. Bath application of phorbol dibutyrate (PDBu, 1 microM) increased the number and opening probability of the InsP3-induced channels.
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PMID:Ca2+-dependent K+ channels in neuroblastoma hybrid cells activated by intracellular inositol trisphosphate and extracellular bradykinin. 326 38

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


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