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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the activity and the ultracytochemical localization of membrane-bound guanylate cyclase (GC) after stimulation with rat atrial natriuretic peptide (rANP), porcine brain natriuretic peptide (pBNP), rat brain natriuretic peptide (rBNP), or porcine C-type natriuretic peptide (CNP) in rat C6 glioma cells during proliferation or following exposure of confluent cells to dibutyryl cyclic AMP (db-cAMP) or retinoic acid (RA). Under our experimental conditions all peptides were activators of GC as demonstrated by the accumulation of cGMP within cells. During proliferation of C6 cells, the amounts of cGMP remained approximately constant. However, at subconfluency, confluency and postconfluency, the GC reaction product was located at different sites in C6 cells. At subconfluency, GC reaction product was on membranes of protoplasmic extensions, at postconfluency, GC reaction product was in association with membranes of cell bodies, and at confluency, both localizations of GC reaction product were detected. Incubation of confluent cells in culture medium containing db-cAMP or RA induced the appearance of long and slender protoplasmic extensions. Under these conditions, the GC reaction product was localized exclusively to these processes. These data suggest that GC is differentially located depending on the state of growth of glial cells, and that in differentiating glial cells GC is preferentially located in cell processes.
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PMID:Detection of membrane-bound guanylate cyclase activity in rat C6 glioma cells at different growth states following activation by natriuretic peptides. 755 44

Characterization of the serotonin-induced increase in guanosine 3',5'-cyclic monophosphate (cyclic GMP) was investigated and compared with that induced by atrial natriuretic peptide (ANP) in NG108-15 cells. The cyclic GMP formed by serotonin or ANP was transported in a similar manner to the extracellular medium, although the cyclic GMP formed by bradykinin was not. Serotonin and ANP raised cyclic GMP additively. Serotonin-induced cyclic GMP formation was completely inhibited by pretreatment with 100 nM 12-o-tetradecanoylphorbol 13-acetate (TPA), although that induced by ANP was only partially inhibited and the effects were blocked by pretreatment with staurosporin. In membrane preparations, ANP stimulated cyclic GMP formation in the presence of ATP, but serotonin did not. Serotonin-stimulated cyclic GMP formation was found to occur in neuroblastoma N18TG-2, but not in glioma C6Bu-1. These results suggest that a novel subtype of serotonin receptors (5-HTGC) which stimulates membrane-bound guanylyl cyclase, different from that stimulated by natriuretic peptide, may exist especially in neurons.
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PMID:Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably through a novel subtype of serotonin receptor (5-HTGC). 853 98

C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, is found throughout the central nervous system (CNS), particularly in those regions involved in neuroendocrine regulation. Astrocytes, which have important physiological roles in normal neuronal functioning, express receptors of CNP. Using reverse transcription-polymerase chain reaction (RT-PCR), followed by hybridization with a digoxigenin-labelled cDNA probe, we have demonstrated the expression of CNP gene transcripts in both cultured mouse astrocytes and rat C6 glioma cells, with the former expressing the gene at a considerably higher level than the latter. Our data raise the possibility that CNP may act in autocrine and/or paracrine fashion in glial cell physiology and neuromodulate communication between glial cells and neurones.
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PMID:Identification of C-type natriuretic peptide gene transcripts in glial cells. 890 48

1. A variety of studies have suggested that K+ channel activity is a key determinant for cell progression through the G1 phase of mitosis. We have previously proposed that K+ channels control the activity of cell cycle-regulating proteins via regulation of cell volume. In order to test this hypothesis, we measured, with a Coulter counter and under different experimental conditions, the volume and rate of proliferation of neuroblastoma x glioma hybrid NG108-15 cells. 2. The K+ channel blockers TEA (1-10 mM), 4-aminopyridine (0.2-2 mM) and Cs+ (2.5-10 mM) increased the cell volume and decreased the rate of cell proliferation. Proliferation was fully inhibited when cell volume was increased by 25 %. 3. A 40 % increase in the culture medium osmolarity with NaCl induced a 25 % increase in cell volume and an 82 % decrease in the rate of cell proliferation. A 40 % increase in the culture medium osmolarity with mannitol induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell proliferation. 4. The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid; 50 microM) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation. 5. A 24 % reduction in the culture medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation. 6. Under whole-cell patch-clamp conditions, antibiotics (penicillin plus streptomycin) decreased the voltage-dependent K+ current. Omission of antibiotics from the culture medium induced a 10 % decrease in the cell volume and a 32 % increase in the rate of cell proliferation. 7. These results suggest that the mechanisms controlling cell proliferation are strongly influenced by the factors which determine cell volume. This could take into account the role in mitogenesis of K+ channels and of other ionic pathways involved in cell volume regulation.
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PMID:K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. 962 69

Recent studies have shown that swelling-activated myo-inositol efflux from rat C6 glioma cells is mediated by a single transport mechanism and most likely by a volume-sensitive anion channel. In those studies, cells were acclimated in hypertonic medium and then swollen by returning the cells to isotonic medium. In the present study, myo-inositol efflux was determined in primary cultures of astrocytes by first incubating the cells in isotonic radiolabelled medium for 2 hr and then placing the cells in either unlabelled isotonic, hypertonic, or hypotonic medium and measuring release with time. Computer analyses of efflux data indicated a two-component system of myo-inositol efflux. The rate constants for the initial fast component for isotonic and hypotonic cells were 0.0398 +/- 0. 005 and 0.0631 +/- 0.0288 min(-1), respectively. The efflux rates of the slow component, while quite small, were severalfold greater with increasing hypotonic media as compared to the cells in isotonic medium. Several anion membrane transport inhibitors were tested to explore the swelling activated efflux mechanism of myo-inositol. Furosemide (0.5 mM), 1,9 dideoxyforskolin (0.1 mM), NPPB (0.1 mM), niflumic acid (0.5 mM), and SITS (0.5 mM) blocked the fast component of myo-inositol efflux by 17, 49, 55, 75, and 93%, respectively. Our results suggest that the fast component of myo-inositol efflux in primary cultures of astrocytes is mediated by anion transporters or channels and that myo-inositol flux contributes to cell volume regulation in cultures of primary astrocytes.
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PMID:Effect of osmolality and anion channel inhibitors on myo-inositol efflux in cultured astrocytes. 1046 58

K+ and Cl- channels are involved in regulating the proliferation of a number of cell types. Two main hypotheses have been proposed to explain the mechanism by which these channels influence cell proliferation: regulation of membrane potential and regulation of cell volume. In order to test these hypotheses, we measured, under different experimental conditions, the volume, membrane potential and rate of proliferation of C6 glioma cells. Cells cultured in control medium for 1-4 days were compared with cells cultured for the same period of time in the presence of broad spectrum channel blockers: tetraethylammonium, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and Cs+, in hypertonic media (29% increased osmolarity with NaCl, KCl or sucrose), in hypotonic medium (23% decreased osmolarity with H2O) or in the presence of the specific channel blockers, i.e. mast cell degranulating peptide, charybdotoxin or chlorotoxin. In all of these conditions, we observed a close correspondence between the rate of proliferation and the mean cell volume. The proliferation decreased when volume increased. Moreover, whereas control cells were flattened, spindle-shaped, bipolar or multipolar, cells cultured in media supplemented with NPPB, KCl or CsCl were round with few processes. Of the agents tested, only KCl and Cs+ depolarized the cells. These results show that alterations of the rate of proliferation by K+ and Cl- channel blockers or anisotonia are closely related with changes in cell volume or form but are not correlated with changes in membrane potential.
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PMID:Control of cell proliferation by cell volume alterations in rat C6 glioma cells. 1104 54

A minireview is presented on the ultracytochemical localization of membrane-bound guanylate cyclase (GC) in various tissues and in cultured cells after activation with three natriuretic peptides, the atrial natriuretic factor (ANF), the brain natriuretic peptide (BNP), and the C-type natriuretic peptide (CNP). GC, two subtypes of which have been recently identified, is the receptor for these peptides. The GC isoforms are differently stimulated by ANF, BNP and CNP. Under our experimental conditions, the natriuretic peptides were strong activators of GC since samples incubated without natriuretic peptides do not reveal any cyclase activity. The natriuretic peptide-stimulated GC activity was studied in rat kidney, lung, adrenal gland and neurohypophysis, in rabbit platelets, in lamb olfactory mucosa, and in rat C6 glioma cells. On the basis of the subcellular GC localization some additional functions of peptides are hypothesized.
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PMID:Membrane-bound guanylate cyclase as the receptor of natriuretic peptides. A minireview. 1132 35

We used an in vitro model for glioma cell invasion (transwell migration assay) and patch-clamp techniques to investigate the role of volume-activated Cl(-) currents (I(Cl,Vol)) in glioma cell invasion. Hypotonic solutions ( approximately 230 mOsm) activated outwardly rectifying currents that reversed near the equilibrium potential for Cl(-) ions (E(Cl)). These currents (I(Cl,Vol)) were sensitive to several known Cl(-) channel inhibitors, including DIDS, tamoxifen, and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The IC(50) for NPPB inhibition of I(Cl,Vol) was 21 microm. Under isotonic conditions, NPPB (165 microm) blocked inward currents (at -40 mV) and increased input resistance in both standard whole-cell recordings and amphotericin perforated-patch recordings. Reducing [Cl(-)](o) under isotonic conditions positively shifted the reversal potential of whole-cell currents. These findings suggest a significant resting Cl(-) conductance in glioma cells. Under isotonic and hypotonic conditions, Cl(-) channels displayed voltage- and time-dependent inactivation and had an I(-) > Cl(-) permeability. To assess the potential role of these channels in cell migration, we studied the chemotactic migration of glioma cells toward laminin or vitronectin in a Boyden chamber containing transwell filters with 8 microm pores. Inhibition of I(Cl,Vol) with NPPB reduced chemotactic migration in a dose-dependent fashion with an IC(50) of 27 microm. Time-lapse video microscopy during patch-clamp recordings revealed visible changes in cell shape and/or movement that accompanied spontaneous activation of I(Cl,Vol), suggesting that I(Cl,Vol) is activated during cell movement, consistent with the effects of NPPB in migration assays. We propose that I(Cl,Vol) contributes to cell shape and volume changes required for glioma cell migration through brain tissue.
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PMID:Volume-activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells. 1156 57

Primary brain tumors (gliomas) often present with peritumoral edema. Their ability to thrive in this osmotically altered environment prompted us to examine volume regulation in human glioma cells, specifically the relative contribution of Cl(-) channels and transporters to this process. After a hyposmotic challenge, cultured astrocytes, D54-MG glioma cells, and glioma cells from human patient biopsies exhibited a regulatory volume decrease (RVD). Although astrocytes were not able to completely reestablish their original prechallenge volumes, glioma cells exhibited complete volume recovery, sometimes recovering to a volume smaller than their original volumes (V(Post-RVD) < V(baseline)). In glioma cells, RVD was largely inhibited by treatment with a combination of Cl(-) channel inhibitors, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and Cd(2+) (V(Post-RVD) > 1.4*V(baseline)). Volume regulation was also attenuated to a lesser degree by the addition of R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA), a known K(+)-Cl(-) cotransporter (KCC) inhibitor. To dissect the relative contribution of channels vs. transporters in RVD, we took advantage of the comparatively high temperature dependence of transport processes vs. channel-mediated diffusion. Cooling D54-MG glioma cells to 15 degrees C resulted in a loss of DIOA-sensitive volume regulation. Moreover, at 15 degrees C, the channel blockers NPPB + Cd(2+) completely inhibited RVD and cells behaved like perfect osmometers. The calculated osmolyte flux during RVD under these experimental conditions suggests that the relative contribution of Cl(-) channels vs. transporters to this process is approximately 60-70% and approximately 30-40%, respectively. Finally, we identified several candidate proteins that may be involved in RVD, including the Cl(-) channels ClC-2, ClC-3, ClC-5, ClC-6, and ClC-7 and the transporters KCC1 and KCC3a.
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PMID:Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells. 1565 14

Neuronal chloride concentration ([Cl(-)](i)) is known to be dynamically modulated and alterations in Cl(-) homeostasis may occur in the brain at physiological and pathological conditions, being also likely involved in glioma-related seizures. However, the mechanism leading to changes in neuronal [Cl(-)](i) during glioma invasion are still unclear. To characterize the potential effect of glioma released soluble factors on neuronal [Cl(-)](i), we used genetically encoded CFP/YFP-based ratiometric Cl-(apical) Sensor transiently expressed in cultured hippocampal neurons. Exposition of neurons to glioma conditioned medium (GCM) caused rapid and transient elevation of [Cl(-)](i), resulting in the increase of fluorescence ratio, which was strongly reduced by blockers of ionotropic glutamate receptors APV and NBQX. Furthermore, in HEK cells expressing GluR1-AMPA receptors, GCM activated ionic currents with efficacy similar to those caused by glutamate, supporting the notion that GCM contains glutamate or glutamatergic agonists, which cause neuronal depolarization, activation of NMDA and AMPA/KA receptors leading to elevation of [Cl(-)](i). Chromatographic analysis of the GCM showed that it contained several aminoacids, including glutamate, whose release from glioma cells did not occur via the most common glial mechanisms of transport, or in response to hypoosmotic stress. GCM also contained glycine, whose action contrasted the glutamate effect. Indeed, strychnine application significantly increased GCM-induced depolarization and [Cl(-)](i) rise. GCM-evoked [Cl(-)](i) elevation was not inhibited by antagonists of Cl(-) transporters and significantly reduced in the presence of anion channels blocker NPPB, suggesting that Cl(-) selective channels are a major route for GCM-induced Cl(-) influx. Altogether, these data show that glioma released aminoacids may dynamically alter Cl(-) equilibrium in surrounding neurons, deeply interfering with their inhibitory balance, likely leading to physiological and pathological consequences.
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PMID:Transient increase in neuronal chloride concentration by neuroactive aminoacids released from glioma cells. 2318 38


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