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)

Ras (p21) proteins are involved in the control of cell growth and differentiation, but the mechanism by which they exert these effects is not yet known. Here we present evidence that c-Ha-ras (p21(Gly-12)) and its oncogenic mutant T24-ras (p21(Val-12)) selectively induce omega-conotoxin and dihydropyridine-sensitive Ca2+ currents within a few hours after introduction into the cytoplasm of neuroblastoma x glioma hybrid cells. Whereas control cells exhibited a mean Ca2+ current of 250 pA, it amounted to 730 pA in cells pretreated with ras protein. In cells loaded with p21(Gly-12), the effect occurred after 2 hours and was terminated after 8 hours. In contrast, introduction of p21(Val-12) resulted in a prolonged delay (6 hours) of the effect which lasted for more than 24 hours. When ras proteins were preactivated with the non-hydrolysable GTP analog GppNHp, the time courses of both p21(Gly-12) and p21(Val-12) effects were fast and sustained, suggesting that in intact cells (i) the GDP/GTP exchange is faster for p21(Gly-12) compared to p21(Val-12) and (ii) inactivation of p21(Gly-12) is mediated by GAP-induced GTPase activity. T-type Ca2+ currents and K+ currents were unaffected by ras proteins.
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PMID:Ras proteins activate calcium channels in neuronal cells. 165 68

The transport of glycine in C6 glioma cells takes place mainly in a heterogeneous Na+-dependent manner which can be resolved into different components. A Na+- and Cl(-)-dependent component with high affinity for glycine is pH-sensitive and inhibited by sarcosine, all these characteristics corresponding to System Gly. The low-affinity component of the transport of glycine can be discriminated as two components, namely System A and System ASC. The main proportion of glycine transport through the low-affinity system is carried out by the ASC System, which appears to be constitutively expressed by the cells. The adaptive response of the low-affinity Na+-dependent transport of glycine to amino acid deprivation was identified with System A on the basis of its ion-dependency, pH-sensitivity and by inhibition analysis. The possible physiological role of the high- and low-affinity components of the transport system for glycine in glial cells is discussed.
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PMID:Characteristics and adaptive regulation of glycine transport in cultured glial cells. 270 91

Tritiated DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr) binds with high affinity, specificity and saturability to neuroblastoma N18TG2 and hybrid neuroblastoma x glioma NG108-15 and NG108-5 intact cells. The delta-opioid receptor density in cells cultured in chemically defined medium was increased about 2 times compared to that in cells cultured in 10% fetal calf serum. A major and a minor protein species covalently and specifically bound to [125I]azido-DTLET (Tyr-D-Thr-Gly-pN3Phe-Leu-Thr), photoactivatable ligand, migrated on SDS-gel electrophoresis with Mr values near 33,000 and 58,000, respectively.
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PMID:Photoaffinity labeling of a 33 kDa protein subunit of the delta-opioid receptor in neuroblastoma and hybrid cell lines. 283 23

Two series of dimeric enkephalin analogues were assayed for opioid activity in two isolated smooth muscle preparations: the guinea pig ileum (GPI) and the mouse vas deferens (MVD). Dimers have the general structure: X-(CH2)n-X, where X is H-Tyr-D-Ala-Gly-Phe-Leu-NH-(n = 0, 2, 4, 6, 8, 10, 12), for the first series of dimeric pentapeptide enkephalins (DPEn), and H-Tyr-D-Ala-Gly-Phe-NH-(n = 2, 4, 6, 8, 12), for the series of dimeric tetrapeptide enkephalins (DTEn). Comparison of biological activities with binding affinities revealed that: (1) the DPE series with n = 2-8 showed increased potency in the MVD assay relative to monomeric [D-Ala2, Leu5]enkephalinamide (DALEA); (2) there was an associated increase affinity for the delta receptor of rat brain or neuroblastoma-glioma hybrid cells. (however, the relative potencies were higher in the MVD assay then predicted on the basis of binding affinities); (3) the DTE series also showed an increase in delta receptor affinities and MVD potencies relative to DALEA, for n = 2-12; (4) for the DTE series, the increase in MVD activities was less than that expected on the basis of delta binding affinity; (5) for both the DPE and DTE series, activities in the GPI assay and mu-receptor affinities were highly correlated: as the length of the methylene bridge increased from 2 to 12, there was a progressive loss of activity in both assays, with a similar pattern for DPE and DTE. Two selected dimers and their corresponding monomers were also assayed for antinociceptive activity in vivo: results were consistent with GPI and mu-binding but not with MVD and delta-binding. Two alkylamide analogs of penta- and tetrapeptide monomers, representing the monomer with the attached spacer of the most active dimers, were also assayed in biological and binding assays. Comparison of these compounds with the corresponding dimers suggest that the changes in activities and selectivities induced by dimerization are not a spurious effect of the presence of an akylamide derivative of the carboxy terminal of enkephalin but rather may represent a specific effect due to the bivalent nature of the ligands.
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PMID:Receptor binding and biological activity of bivalent enkephalins. 298 28

The binding of alkylendiamide dimers of the three N-terminal residues of [D-Ala2,D-Leu5]enkephalin (DADL) to rat brain and Ng108-15 neuroblastoma-glioma cell membranes was compared with that of DADL, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and morphiceptin. Tritiated DADL and DAGO were used as labeled ligands for delta- and mu-receptors, respectively. Dimerization of the tripeptides resulted in dramatic increases in both mu and delta binding. The binding to mu-receptors showed two peaks at an alkyl chain length of n = 2 and approximately n = 16. In contrast, delta binding (NG108-15 cells) increased steadily with increasing chain length. The dimers with n less than 18 were mu-preferential, and the one with n = 2 showed the most dramatic increase in mu selectivity with a 400 fold higher affinity to mu- than to delta-receptors. For long-chain alkyl spacers the compounds became delta selective.
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PMID:Increased affinity and selectivity of enkephalin tripeptide (Tyr-D-Ala-Gly) dimers. 299 Sep 53

Iodinated human beta-endorphin was affinity-cross-linked to opioid receptors present in membrane preparations from bovine frontal cortex, bovine striatum, guinea pig whole brain, and rat thalamus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed covalently labeled peptides of 65, 53, 41, and 38 kilodaltons (kDa). The 65- and 38-kDa peptides were present in all four tissues. The 41-kDa peptide was seen only in bovine caudate and guinea pig whole brain while the 53-kDa peptide was absent in rat thalamus. All four labeled peptides were constituents of opioid receptors since their labeling was fully suppressed by the presence of excess opiates, such as bremazocine, during binding. The distribution and levels of the labeled species in the brain tissues examined and, in earlier work, in the neuroblastoma X glioma NG 108-15 cell line suggested that the 65-kDa peptide is a binding component of mu receptors while the 53-kDa peptide is a binding subunit of delta receptors. This result was strongly supported by the finding that the labeling of the 65-kDa peptide is selectively reduced by the presence of the highly mu-selective ligand Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol (DAMGE) during binding, while while the labeling of the 53-kDa peptide is selectively reduced or eliminated by the highly mu-selective ligand [D-Pen2, D-Pen5]enkephalin (DPDPE). The labeling of the 41- and 38-kDa bands was reduced by either DAMGE or DPDPE. The relationship of these lower molecular weight opioid-binding peptides to mu and delta receptors is not understood. Several possible explanations are presented.
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PMID:Identification of distinct binding site subunits of mu and delta opioid receptors. 300 57

Receptor subclass recognition properties of affinity-purified rabbit polyclonal anti-idiotypic anti-opiate receptor antibodies in various membrane preparations have been determined. The anti-receptor immunoglobulins significantly decrease binding of 3H-[D-Ala2,-MePhe4,Gly-ol5]enkephalin, a highly selective mu agonist, in rat neural membrane. In the presence of a concentration of the unlabeled ligand sufficient to block existing mu sites, the antibodies compete, to a lesser degree with 3H-[D-Ala2,D-Leu5]enkephalin for delta site occupancy in both rat neural membrane, and neuroblastoma x glioma membrane preparations. The antibodies do not displace 3H-ethylketocyclazocine from rat brain or guinea pig cerebellum.
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PMID:Subclass specificity of anti-idiotypic anti-opiate receptor antibodies in rat brain, guinea pig cerebellum, & neuroblastoma x glioma (NG 108-15). 301 23

The effect of opioids on phosphatidylinositol (PI) turnover to release inositol triphosphate (IP3) as second messenger was examined in mouse neuroblastoma X rat glioma hybrid cells NG108-15 (delta-receptors) and human neuroblastoma cells, SK-N-SH (predominantly mu-receptors). PI turnover can be stimulated in both NG108-15 and SK-N-SH cells by bradykinin and acetylcholine, respectively. In contrast, etorphine, DADL ([D-Ala2,D-Leu5]-enkephalin) and DAGO ([D-Ala2,MePhe4,Gly-ol5]-enkephalin), up to 1 microM concentrations failed to affect PI turnover in both cell lines. These results suggest that IP3 is not likely to serve as second messenger for both mu- and delta-opioid receptors.
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PMID:Phosphatidylinositol turnover in neuroblastoma cells: regulation by bradykinin, acetylcholine, but not mu- and delta-opioid receptors. 302 76

[3H]Az-DTLET (Tyr-D-Thr-Gly-Phe(pN3)-Leu-Thr), a photoaffinity probe for delta opioid receptors binds to a single class of sites in rat brain membranes with a high affinity (KD = 1.66 nM). The selectivity index of Az-DTLET (KI delta/KI mu = 0.036) is better than that of its precursor DTLET (0.053). Rat brain or neuroblastoma glioma cells membranes were incubated with 10 nM [3H]Az-DTLET, washed and irradiated with U.V. After irradiation a fraction (20-30%) of specific binding was found to remain indissociable after 10 min at 60 degrees C and was considered as irreversible. This fraction increased as a function of the irradiation time. The radioactivity irreversibly bound to rat brain membranes, solubilized by sodium cholate, was associated with high molecular weight species (200,000 daltons). In denaturing conditions (SDS 2%), the [3H]Az-DTLET specific binding was associated with molecular components of 45-50 K and 90-100 K daltons. In contrast, when opioid receptors were prelabelled by [3H]Az-DTLET, solubilized by Na-cholate and irradiated, the radioactivity was only recovered with subunits of 45-50 K daltons. The autoradiographic localization of the irreversibly bound [3H]Az-DTLET in rat brain was identical to that of reversibly bound [3H]DTLET or [3H]Az-DTLET. These results suggest that [3H]Az-DTLET represents an adequate specific probe for studies on the structure, function and anatomical distribution at light and even electron microscopic level of delta-opioid receptors.
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PMID:Irreversible labelling of delta-opioid receptors in rat brain and neuroblastoma cells by [3H]azido-DTLET: characterization of subunits and autoradiographic visualization of the covalent binding. 303 96

To promote neurite elongation, nerve growth cones must adhere to other surfaces. A complex of integral membrane glycoproteins mediates cell binding to the extracellular glycoproteins fibronectin and laminin (Horwitz et al., J Cell Biol 101:2134-2144, 1985). The receptor complex, named integrin, binds to fibronectin by recognition of a specific peptide sequence, Arg-Gly-Asp-Ser (RGDS), in the fibronectin molecule (Pierschbacher and Ruoslahti, Proc Natl Acad Sci USA 81:5985-5988, 1984). We have used antibodies to integrin and an RGDS synthetic peptide to probe the functions of integrin in the migration of growth cones extended from sensory and spinal cord neurons of chick embryos. Analyses of time lapse videotapes of growth cone migration before and after adding RGDS indicated that 2 mM RGDS rapidly inhibits growth cone movement on substrata coated with fibronectin or a fragment of fibronectin containing the RGDS sequence. RGDS has no effect on growth cone movement on laminin or on a surface coated with material deposited from heart conditioned medium. However, a monclonal antibody to the integrin complex (10 micrograms/ml CSAT) completely blocks growth cone movement on substrata treated with fibronectin, laminin, or heart conditioned medium. Thus integrin may be involved in growth cone adhesion to several extracellular molecules, although the selective effects of RGDS indicate that the integrin complex may have heterogeneous sites for interaction with different components of the extracellular matrix. CSAT antibody has no discernible effect, however, on growth cone migration across the upper surfaces of C6 glioma cells. These data indicate that the surfaces of nerve growth cones contain multiple binding molecules that mediate different adhesive interactions during migration.
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PMID:Growth cone migration across extracellular matrix components depends on integrin, but migration across glioma cells does not. 326 60


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