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 ultimate purpose of the present study was to evaluate correlations between acute in vivo and in vitro toxicity and log P (P is n-octanol-water partition coefficient). The in vitro toxicity to cloned cells (neuroblastoma N18TG-2 and glioma C6) in culture (ED50) and the in vivo toxicity to mice (LD50) of ethylene glycol ethers were studied in terms of the structure-activity relationship. The test ethers showed a wide range of ED50 values in both cells. LD50 was determined under two conditions: LD50-cont. was estimated in mice pretreated with olive oil and LD50-CCl4 in CCl4-pretreated mice. Multiple regression analyses revealed a significant correlation between log 1/LD50 and log P as follows: log (1/LD50-cont.) = -0.120 (log P)2+0.487log P-1.182, and log (1/LD50-CCl4) = -0.128 (log P)2+0.566log P-1.157. There was no significant correlation either between ED50 and LD50 or between ED50 for N18TG-2 and ED50 for C6. The results suggest that metabolic activation might not occur during acute toxicity from the ethers, and that hydrophobicity, expressed as log P, plays an important role in acute toxicity.
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PMID:Structure-toxicity relationship of ethylene glycol ethers. 161 Mar

In synaptosomal membranes from rat brain cortex, the mu selective agonist [3H]dihydromorphine in the absence of sodium, and the nonselective antagonist [3H]naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with Kd values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 microM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP[gamma-35S] binding sites by 90% and low Km, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP[gamma S] was diminished. High-affinity (Kd, 0.72 nM), guanine nucleotide-sensitive agonist binding was reconstituted by polyethylene glycol-induced fusion of the alkali-treated membranes with (opioid receptor devoid) C6 glioma cell membranes. Also restored was opioid agonist-stimulated, naltrexone-inhibited GTPase activity. In contrast, antagonist binding in the fused membranes was unaltered. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low Km GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor-guanine nucleotide binding protein complex.
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PMID:Reconstitution of high-affinity opioid agonist binding in brain membranes. 184 95

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

Opiate receptor-mediated inhibition of adenylate cyclase activity was elicited in membranes of C6BUI glioma cells and S49 cyc- lymphoma cells after fusion with opiate receptor-containing membranes derived from NG108-15 neuroblastoma x glioma hybrid cells. The fusion was induced by polyethylene glycol using procedures developed by Orly and Schramm [(1976) Proc. Natl. Acad. Sci. USA 73, 4410-4414]. Prior to fusion, the adenylate cyclase activity of the donor. NG108-15 cell membrane, was inactivated by N-ethylmaleimide treatment. Prostaglandin E1 receptors and the stimulatory GTP-binding protein Ns were transferred to the recipient cells along with opiate receptors. Thus, inhibitory receptors can be transferred to foreign adenylate cyclase systems just as stimulatory receptors had earlier been found to do. Furthermore, opiate receptors have been shown to function in non-neuronal cells.
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PMID:Transfer of functional opiate receptors from membranes to recipient cells by polyethylene glycol-induced fusion. 282 Aug 7

Exposure of rat glioma C6 cells to either isoproterenol or 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in desensitization of isoproterenol-stimulated adenylate cyclase activity. After either treatment, the affinity of beta-receptors for isoproterenol was reduced. Thus, desensitization by TPA or isoproterenol appeared to involve an "uncoupling" of the beta-receptor from the stimulatory regulatory component (Ns) of adenylate cyclase. The activity of Ns, assayed by reconstitution of S49 cyc- adenylate cyclase activity, was found to be unchanged after desensitization. The activity of beta-receptors was measured by inactivating Ns and the catalytic component of adenylate cyclase in C6 membranes and fusing them with membranes lacking beta-receptors. Receptors from isoproterenol-treated C6 cells were less active in "coupling" to the foreign adenylate cyclase than receptors from untreated cells, whereas receptors from TPA-treated cells were fully active. This unexpected latter result was explored further. Lysates from C6 cells were centrifuged on linear sucrose density gradients and the gradient fractions assayed for beta-receptor binding activity. Most of the receptors were recovered in a "heavy" plasma membrane peak but some receptors also appeared in a "light" membrane peak. After treatment of the cells with isoproterenol or TPA, the proportion of receptors in the light peak increased. Prior treatment of the cells with concanavalin A prevented the increase in light receptors caused by isoproterenol or TPA. In addition, the concanavalin A treatment prevented the desensitization of adenylate cyclase caused by TPA but not that caused by isoproterenol. Finally, desensitization of adenylate cyclase was reversed by polyethylene glycol-induced fusion of membranes from cells treated with TPA but not isoproterenol. We conclude that beta-agonists and phorbol esters desensitize adenylate cyclase by distinct mechanisms. Agonists cause a reduction in the functional activity of the beta-receptors followed by a segregation of the receptors into a light membrane fraction devoid of Ns. Phorbol esters do not alter the activity of the receptors but do cause their segregation.
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PMID:Phorbol esters and beta-adrenergic agonists mediate desensitization of adenylate cyclase in rat glioma C6 cells by distinct mechanisms. 286 42

Human A431 and rat glioma C6 cells exposed to isoproterenol underwent a time- and dose-dependent loss of isoproterenol-stimulated adenylate cyclase activity. Desensitization was accompanied by sequestration of beta-adrenergic receptors, which became less accessible to the hydrophilic antagonist 3H-labeled 4-(3-tert-butylamino-2-hydroxypropoxy)benzimidazole-2-one hydrochloride ([3H]CGP-12177) and redistributed from the heavier density plasma membrane fraction to a lighter density membrane fraction. Prior treatment of the cells with concanavalin A or phenylarsine oxide blocked sequestration of the receptors but not desensitization of the agonist-stimulated adenylate cyclase. The membranes from such pretreated cells were exposed to alkali to inactivate adenylate cyclase, and the receptors were transferred to a foreign adenylate cyclase by membrane fusion with polyethylene glycol. beta receptors from desensitized cells exhibited a reduced ability to maximally stimulate the foreign adenylate cyclase, but remained accessible to [3H]CGP-12177 in the fused membranes. When isoproterenol-treated cells were washed free of agonist, there was a time-dependent recovery of agonist responsiveness and [3H]CGP-12177-binding sites. Using the fusion technique, the receptors recovered their functional activity in the resensitized cells. In concanavalin A-treated cells, desensitization and resensitization appeared to occur in the absence of receptor sequestration. Finally, membranes from desensitized cells pretreated with concanavalin A were fused with polyethylene glycol and assayed for agonist-stimulated adenylate cyclase. There was no reversal of the desensitized state. Thus, the primary, essential step in the desensitization process is a reduction in functional activity of the beta-adrenergic receptor. In contrast, sequestration of the receptors is not a prerequisite, but a secondary event during desensitization.
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PMID:Desensitization of the beta-adrenergic receptor-coupled adenylate cyclase in cultured mammalian cells. Receptor sequestration versus receptor function. 301 67

Our studies demonstrate that rat anterior pituitary cells (GH3) are capable of synthesizing and secreting tissue kallikrein together with prolactin and growth hormone. The secretion of prolactin and growth hormone in GH3 cells was measured by two newly developed sensitive radioimmunoassays (RIA), using the polyethylene glycol separation technique. In the direct radioimmunoassay for rat tissue kallikrein, using a polyclonal antiserum which recognizes both active and prokallikrein, the GH3 kallikrein displays parallelism with standard curves of rat urinary kallikrein. The production of immunoreactive kallikrein, prolactin, and growth hormone is time-dependent, and the levels after a 72 h incubation in serum-free media are approximately 12.2 +/- 4.4 ng, 272.2 +/- 33.0 ng, and 475.6 +/- 4.8 ng per 10(6) cells per ml (mean +/- SD, n = 3), respectively. In Western blot analyses, a specific monoclonal antibody to tissue kallikrein (V4D11) identifies GH3-secreted kallikrein as a approximately 39,000 Da protein, slightly larger than approximately 38,000 Da kallikreins of submandibular gland, mouse anterior pituitary cells (AtT 20) or rodent neuroblastoma X glioma hybrid cells (NG108). Kallikrein mRNA in GH3 cells was identified in Northern blot analyses, using a tissue kallikrein cDNA probe. In a RIA using a kallikrein monoclonal antibody (V1C3) recognizing only active kallikrein, kallikrein could not be detected in the media incubated up to 48 h with GH3 cells. However, after trypsin treatment, a time-dependent increase of immunoreactive kallikrein (using monoclonal antibody V1C3), Tos-Arg-OMe esterase, and kinin-releasing activities can be measured in the conditioned media. The activated esterase activity was inhibited by aprotinin and by affinity-purified kallikrein monoclonal antibody (V4D11) in a dose-dependent manner. The data indicated that rat anterior pituitary GH3 cells secrete latent tissue kallikrein, which can be converted to active kallikrein by trypsin. These hormonally responsive cells co-synthesize kallikrein with prolactin and growth hormone and provide a model system for studying the regulation of kallikrein gene expression.
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PMID:Identification of latent tissue kallikrein, prolactin and growth hormone secretion in GH3 pituitary cells using modified radioimmunoassays. 336 Feb 6

Severed medial giant axons in crayfish can be rejoined in vitro with polyethylene glycol (PEG) to produce axoplasmic continuity and through transmission of action potentials. Severed axon-like processes of a mammalian neuroblastoma/glioma cell line seem to be rejoined to the cell body using PEG in tissue culture. Our data suggest that PEG might be used to rejoin severed axons in vivo in various organisms.
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PMID:Reconnection of severed nerve axons with polyethylene glycol. 369 10

The incorporation of methionine, lysine, and leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of C-6 glial tumor cells in minimal medium. Although incorporation proceeded at linear rates in both preparations for more than 1 h and into the same spectrum of proteins, Ca2+-restored cells incorporated amino acid 5- to 10-fold more rapidly than Ca2+-depleted cells. Addition of approximately 200 microM Ca2+ in excess of chelator was required to achieve maximal rates of incorporation in Ca2+-depleted preparations. Stimulation by Ca2+ was rapid in onset (several minutes) and slowly reversible by chelator. Ca2+ was uniquely potent and specific among physiologically occurring cations in conferring such stimulation. Stimulation of amino acid incorporation by Ca2+ occurred over a broad range of pH and osmolarities and was facilitated by Mg2+. The effects of Ca2+ in stimulating amino acid incorporation were not traceable to changes in cAMP metabolism, amino acid uptake, protein catabolism, cell ATP or GTP content, or aminoacylation of transfer RNA. Actinomycin D (1 microgram/ml) did not block the stimulatory effects of Ca2+ although puromycin and cycloheximide did. The stimulatory effects of Ca2+ on protein synthesis were not restricted to C-6 in minimal medium. Protein synthesis was reduced by ethylene glycol bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid 40 to 75% in C-6 glioma, GH3 pituitary tumor, PC-12 adrenal tumor, N2A neuroblastoma, and HeLa cells incubated under simulated growth conditions with various enriched media and sera. Ca2+-depleted S49 lymphoma, CHO ovarian tumor, and normal, dispersed chicken embryo cells in enriched medium responded to Ca2+ restoration with increased rates of protein synthesis as did collagenase-dispersed normal rat liver cells in minimal medium. Protein synthesis in rabbit reticulocyte lysates was also inhibited by Ca2+-selective chelators or by Ca2+ removal by parvalbumin affinity chromatography and the inhibition was reversed by Ca2+. These findings are consistent with the existence of a Ca2+ requirement in the translational phase of protein synthesis in eukaryotic cells.
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PMID:Identification of a Ca2+ requirement for protein synthesis in eukaryotic cells. 631 27

Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce the proliferation of glioma cells in vitro. Trapidil and suramin inhibit this growth factor-stimulated glioma cell growth, but the mechanisms are not fully understood. The effects of trapidil and suramin on PDGF- and EGF-induced early biochemical events in T98G cells were studied. PDGF induced a rapid increase of intracellular free calcium concentration ([Ca2+]i) in fura-2/acetoxymethyl ester-loaded single glioma (T98G) cells. This increase was completely inhibited by removal of extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)-N,N,N,N-tetraacetic acid but not by an L-type calcium channel blocker (nicardipine), suggesting that PDGF may cause calcium influx through voltage-independent calcium channels in T98G cells. Trapidil and suramin blocked the PDGF-induced calcium response and inhibited the PDGF-initiated tyrosine phosphorylation of the PDGF receptor as detected by Western blot analysis using an antibody specific for phosphotyrosine. Trapidil and suramin also inhibited EGF-initiated calcium response in T98G cells, but only partially inhibited EGF-initiated tyrosine phosphorylation at the same concentrations. Our results suggest that trapidil and suramin inhibit PDGF- and EGF-initiated early biochemical events, and thus suppress growth factor-induced cell proliferation.
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PMID:Effects of trapidil and suramin on growth factor-induced calcium response and tyrosine phosphorylation in human glioma cells. 756 95


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