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)

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

Confocal fluorescence microscopy was used to study the bradykinin-induced calcium signals in the neuroblastoma x glioma cell line NG 108-15. We found that bradykinin induced a rise in free calcium, not only in the cytoplasm but also in the nucleus. The nuclear and cytosolic calcium concentrations were not significantly different and rose to about 1.2 microM. The signal was mediated by the B2-receptor subtype as confirmed using the specific antagonist Hoe 140. Both the onset and the intensity of the calcium signals were concentration-dependent. The rise of nuclear calcium level was independent of extracellular calcium and suppressed by thapsigargin which is known to deplete inositol 1,4,5-trisphosphate-sensitive calcium stores. Bradykinin-induced calcium increase desensitizes rapidly. This desensitization was shown not to involve activation of protein kinase C.
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PMID:Bradykinin induces rise of free calcium in nuclei of neuroblastoma x glioma hybrid NG 108-15 cells. 760 11

Transfection of a human dopamine D3 receptor cDNA in a neuroblastoma-glioma hybrid cell line (NG 108-15) provided clonal cell lines stably expressing up to 600 fmol per mg protein of [125I]iodosulpiride binding sites. Dopamine and several agonists distinguished two receptor-affinity states in membranes. In the case of dopamine, the high-affinity state (Ki = 0.9 nM, 30% of total binding) was completely converted into a low-affinity state (Ki = 57 nM) in the presence of 10 microM guanosine-5'-O-(3-thiotriphosphate). In addition to these two sites, a site with a very low affinity for dopamine was evidenced in whole cells. The dopamine D3 receptor mediated two responses: c-fos activation, as measured by the appearance of Fos-like immunoreactivity, and increased mitogenesis, as measured by incorporation of [3H]thymidine. The Fos-like immunoreactivity appeared within 30 min, lasted 2 h and was blocked by the partially selective dopamine D3 receptor compound (+)-UH 232 (cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin). The mitogenic effect, which occurred after a lag time (over 2 h stimulation), was produced with subnanomolar potency and full intrinsic activity by several compounds previously identified as dopamine D2 receptor agonists, e.g. quinpirole, (+)-7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and RU 24926 (N-n-propyl-di-beta(3-hydroxyphenyl)-ethylamine), and was reversibly blocked by (+)-UH 232 (Ki = 9 nM). Talipexole (B-HT 920, 5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin) was identified as a partial agonist at the dopamine D3 receptor. Dopamine D3 receptor-mediated mitogenesis was potentiated by a phorbol ester and was abolished by pretreatment with pertussis toxin. A mitogenic effect of same amplitude was elicited by bradykinin or carbachol, both acting through constitutive receptors. Bradykinin markedly activated inositol phosphate turnover, and had no effect on forskolin-stimulated cyclic AMP accumulation. Carbachol inhibited forskolin-stimulated cyclic AMP accumulation and had no effect on inositol-phosphate turnover. Quinpirole had no effect on any of these second messenger pathways. Thus, in transfected NG 108-15 cells, the dopamine D3 receptor is coupled to a pertussis toxin-sensitive G protein and mediates two possibly unrelated biological effects, through initial biochemical events that remain to be identified.
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PMID:Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line. 795 35

Bradykinin, infused in low doses (10 micrograms/kg/min) through the carotid artery ipsilateral to RG2 glioma in rats, significantly increased the permeability in tumor capillaries to six different tracers of varying molecular weights compared with intracarotid infusion of saline alone. Permeability in normal brain capillaries was not significantly increased by intracarotid bradykinin infusion. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horseradish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant K(i) (microliter/g/min). The permeabilities (K(i)) of tumors in the bradykinin group versus the control saline group for AIB, sucrose, inulin, and dextran were 25.91 +/- 6.78 vs. 13.95 +/- 4.29 (p < 0.01), 17.90 +/- 2.65 vs. 10.75 +/- 4.55 (p < 0.01), 23.92 +/- 6.99 vs. 6.20 +/- 4.37 (p < 0.01), and 17.84 +/- 1.00 vs. 1.47 +/- 1.24 (p < 0.001), respectively (mean +/- SD). Permeability of RG2 gliomas to high molecular weight dextran (70,000) was 12-fold higher in the bradykinin group than in the saline infusion group. Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. The permeability of normal brain capillaries was unaffected by intracarotid bradykinin infusion. The increased permeability was reversed 20 min after stopping the intracarotid infusion. Electron microscopic and gross qualitative analysis was performed using HRP and EB. Intracarotid bradykinin infusion increased HRP and EB within tumor tissue but not normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bradykinin selectively opens blood-tumor barrier in experimental brain tumors. 806 81

Opioids elicit an increase in the intracellular free Ca2+ concentration ([Ca2+]i) in neuroblastoma x glioma hybrid NG108-15 cells, which, depending upon growth conditions, results from either Ca2+ influx in differentiated cells or Ca2+ release from internal stores in undifferentiated cells (Jin et al., 1992). In this report we describe fura-2-based digital imaging studies that demonstrate that opioid-evoked Ca2+ release in these cells results from the activation of phospholipase C (PLC) and subsequent mobilization of the inositol 1,4,5-trisphosphate (IP3)-sensitive store. D-Ala2-D-Leu5-enkephalin (DA-DLE) evoked concentration-dependent increases in [Ca2+]i (EC50 approximately equal to 4 nM). The response was blocked by naloxone (1 microM). In single cells, sequential application of selective opioid agonists (10 nM) evoked responses of the rank order DADLE = D-Pen2, D-Pen5-enkephalin (DPDPE) > trans-(+/-) 3,4-dichloro-N-methyl-N-(2-[1- pyrrolidinyl]cyclohexyl) benzeneacetamide (U50488) > D-ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO), consistent with activation of a delta-opioid receptor. Forty percent (n = 198) of the cells responded to 100 nM DADLE with a net [Ca2+]i increase of 483 +/- 40 nM. Bradykinin (100 nM) elicited a response in 91% of the cells with a mean net amplitude of 707 +/- 36 nM. The DADLE-evoked responses were not blocked by removal of extracellular Ca2+; instead, they were abolished by treatment with 10 nM thapsigargin, an agent that depletes and prevents refilling of IP3-sensitive Ca2+ stores. A 1 microM concentration of U73122, an aminosteroid inhibitor of PLC, completely blocked the DADLE-evoked [Ca2+]i increase, while an inactive analog, U73433, was without effect. To explore the possible role of G-proteins in mediating opioid-induced [Ca2+]i increases in NG108-15 cells, we pretreated cells with pertussis or cholera toxin; pertussis toxin blocked the opioid-induced response while cholera toxin was without effect, consistent with a Gi- or Go-mediated effect. Activation of the opioid inhibitory pathway previously described for these cells appears to stimulate the phosphoinositide (PI) cascade as well. Including the PI cascade among the multiple second messenger systems modulated by opioids may be key to understanding the biochemical events that underlie acute and chronic opioid action.
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PMID:Opioids mobilize calcium from inositol 1,4,5-trisphosphate-sensitive stores in NG108-15 cells. 815 47

The effect of heat shock on agonist-stimulated intracellular Ca2+ mobilization and the expression of heat shock protein 72 (hsp72) in neuroblastoma x glioma hybrid cells (NG 108-15 cells) were examined. Hsp72 was expressed at 6 h after heat shock (42.5 degrees C, 2 h), reached a maximum at 12 h, and decreased thereafter. Bradykinin-induced [Ca2+]i rise was attenuated to 28% of control by heat shock at 2 h after heat shock, and reversion to the control level was seen 12 h later. When the cells were treated with quercetin or antisense oligodeoxyribonucleotide against hsp72 cDNA, the synthesis of hsp72 was not induced by heat shock, whereas bradykinin-induced [Ca2+]i rise was abolished and the [Ca2+]i rise was not restored. Recovery from this stressed condition was evident when cells were stimulated by the Ca(2+)-ATPase inhibitor thapsigargin, even in the presence of either quercetin or antisense oligodeoxyribonucleotide. Inositol 1,4,5-trisphosphate (IP3) production was not altered by heat shock at 12 h after heat shock, whereas IP3 receptor binding activity was reduced to 45.3%. In the presence of quercetin or antisense oligodeoxyribonucleotide, IP3 receptor binding activity decreased and reached 27.2% of the control 12 h after heat shock. Our working thesis is that heat shock transiently suppresses the IP3-mediated intracellular Ca2+ signal transduction system and that hsp72 is involved in the recovery of bradykinin-induced [Ca2+]i rise.
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PMID:Effect of heat shock on intracellular calcium mobilization in neuroblastoma x glioma hybrid cells. 818 35

1. A glial cell line derived from C6 rat glioma cells has been shown previously to respond to extracellular pulses of bradykinin or intracellular injection of inositol 1,4,5-trisphosphate (Ins-P3) with a slow hyperpolarizing response due to activation of a K+ current (G. Reiser et al., Brain Res. 506, 205-214; 1990). 2. We determined the ensuing single-channel activity, which is most likely caused by Ca2+ released from internal stores after bradykinin stimulation. Bradykinin-activated channels were selectively permeable to K+, but not to Na+ or to Cl-, and exhibited conductances of mainly 40 and 50 pS. In glioma cells the same type of channel was activated by intracellular injection of Ins-P3 and by extracellular bradykinin pulses.
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PMID:Ca(2+)-dependent K+ channel activity in rat glioma cells induced by bradykinin stimulation and by inositol 1,4,5-trisphosphate injection. 819 79

1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin-induced PLC activation and IK(Ca), but not IM inhibition. (b) This indicates that the transient outward current IK(Ca), but not the decrease of IM in response to bradykinin, is mediated by PLC. (c) U73122 itself inhibits IM and mobilizes Ca2+ from intracellular stores. (d) Externally applied neomycin is not an effective inhibitor of PLC-mediated signalling pathways in NG108-15 cells.
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PMID:The effects of bradykinin on K+ currents in NG108-15 cells treated with U73122, a phospholipase C inhibitor, or neomycin. 913 90

The bradykinin regulation of calcium channel currents in NG108-15 neuroblastoma x glioma hybrid cells was examined, in order to determine: (1) which type of bradykinin receptors mediates the inhibition of N-type calcium channels in these cells; and (2) whether bradykinin can modulate other types of calcium channels in these cells. Bradykinin inhibited both N- and L-type calcium channels in NG108-15 cells, with EC50S of 10 +/- 2 nM and 29 +/- 7 nM, respectively. The inhibition of both L- and N-type calcium channels by bradykinin (100 nM) could be completely inhibited by the bradykinin B2 receptor antagonist Hoe 140 (10 nM). Bradykinin appeared to inhibit that portion of the L-type calcium channel current that was also reversibly inhibited by omega-conotoxin GVIA. The bradykinin inhibition of the L-type calcium channel current was partly reduced by pretreatment of the cells with pertussis toxin, whereas the inhibition of the N-type current was pertussis toxin-insensitive. In some cultures it was observed that the bradykinin B1 receptor agonist desArg9bradykinin inhibited the L-type calcium channel current.
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PMID:Bradykinin inhibition of N- and L-type calcium channel currents in NG108-15 cells. 914 48

Intracarotid low dose bradykinin infusion can selectively increase permeability in brain tumor capillaries. However, the mechanism by which bradykinin selectively increases transport into brain tumors and not normal brain has not been clearly defined. This study therefore sought to determine whether the mechanism by which bradykinin increases tumor permeability specifically involves the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27 Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [14C] sucrose was determined using quantitative autoradiography. Bradykinin (10 microg kg-1 min-1) increased the transport of sucrose to tumors 2.1-fold compared to saline infusion alone (p<0.001). The uptake of sucrose in tumors was significantly inhibited by the bradykinin B2 receptor antagonist, d-Arg, [Hyp3, Thi5,8, d-Phe7]-bradykinin (p<0.01), but not by the B1 receptor antagonist, des-Arg9, [Leu8]-bradykinin. The distribution of B2 receptors in normal brain and tumor tissue was examined by immunohistochemistry using the B2 receptor antiserum, AS 424. High levels of B2 receptors were detected in intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal brain tissue. These results indicate that the permeabilizing effects of bradykinin are mediated through bradykinin B2 receptors, and that differences in distribution of B2 receptors between tumor tissue and normal brain may be responsible for the selective effects on tumor tissue.
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PMID:Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas. 959 2


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