Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurological improvement in brain-tumor patients treated with dexamethasone (DEX) precedes a reduction in peritumor brain edema. In the study reported here, levels of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT), homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA) and tissue water content were measured in grey and white matter adjacent to a 9L glioma in the cat to study DEX-neurotransmitter interactions as possible mechanisms for the acute neurological effects of DEX. Tumor-bearing and control cats were treated or not treated with DEX (0.25 mg/kg IV, 0.25 mg/kg IM) with 0.25 mg/kg IM repeated once (DEX 1) or 3 times (DEX 2) 6 hr apart. In control animals DEX 1 treatment led to significant decreases in concentration of DOPAC; DEX 2 treatment led to increases in HVA and 5-HIAA. Peritumor grey matter from untreated tumor-bearing animals had decreased levels of NA and DA and the metabolite DOPAC with no changes in 5-HT and 5-HIAA. DEX 2 but not DEX 1 resulted in a normalization (increase) in peritumor levels of DA and DOPAC. Neither dose of DEX reduced white matter edema. These findings suggest that the acute beneficial effect of DEX on neurological status may be due to alleviation of neurotransmitter amine and metabolite depletion.
 ...
PMID:Effect of dexamethasone on monoamine and metabolite levels in a brain-tumor model. 246 98

Rat C6 glioma cells were cultured for 4 days in MEM medium supplemented with 10% bovine serum and Na+, K+-ATPase activity was determined in homogenates of harvested cells. Approximately 50% of enzyme activity was attained at 1.5 mM K+ and the maximum (2.76 +/- 0.13 mumol Pi/h/mg protein) at 5 mM K+. The specific activity of Na+, K+-ATPase was not influenced by freezing the homogenates or cell suspensions before the enzyme assay. Ten minutes' exposure of glioma cells to 10(-4) or 10(-5) M noradrenaline (NA) remained without any effect on NA+, K+-ATPase activity. Neither did the presence of NA in the incubation medium, during the enzyme assay, influence the enzyme activity. The nonresponsiveness of Na+, K+-ATPase of C6 glioma cells to NA is consistent with the assumption that alpha (+) form of the enzyme may be preferentially sensitive to noradrenaline. Na+, K+-ATPase was inhibited in a dose-dependent manner by vanadate and 50% inhibition was achieved at 2 x 10(-7) M concentration. In spite of the fact that Na+, K+-ATPase of glioma cells was not responsive to NA, the latter could at least partially reverse vanadate-induced inhibition of the enzyme. Although the present results concern transformed glial cells, they suggest the possibility that inhibition of glial Na+, K+-ATPase may contribute to the previously reported inhibition by vanadate of Na+, K+-ATPase of the whole brain tissue.
 ...
PMID:Na+, K+-ATPase activity in cultured C6 glioma cells. 254 85

The presence of a brain tumor alters regional cerebral blood flow, oxygen consumption, and glucose utilization in adjacent and remote brain tissue, but its effect on brain neurotransmitter levels is unclear. In the present report, the levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in tumor tissue and gray and white matter obtained from cats with induced brain tumors were measured. Glioma cells (9L) were xenotransplanted into the central white matter of the right hemisphere, and 15 d later the brains were frozen in vivo. Samples of tumor, parietal (peritumor), temporal, and frontal gray and white matter were divided for analysis of water content and quantification of amines and their metabolites. The water content of white matter, but not gray matter, adjacent to the tumor was increased. Neurotransmitter amine and metabolite levels were much lower in the tumor than in brain tissue. In gray matter adjacent to the tumor, concentrations of DA and its metabolites HVA and DOPAC were significantly decreased from control, whereas 5-HIAA was increased. The NA, DA, HVA, and DOPAC levels were decreased in temporal gray matter, whereas all amine and metabolite levels were unchanged in frontal gray matter. These results indicate that altered neurotransmitter metabolism is one of the effects of the presence of a brain tumor.
 ...
PMID:Regional monoamine and metabolite levels in a feline brain tumor model. 274 38

The regulation of cytoplasmic pH (pHi) was examined in neuroblastoma X glioma hybrid cell-line cells (NG108-15 cells) using 2,7-biscarboxyethyl-5(6)-carboxyfluorescein. The pHi of NG108-15 cells suspended in nominally HCO-3-free, Na+-containing buffer could be reduced by the external application of acetate. The recovery of pHi to its resting value was blocked by the removal of extracellular Na+, by the addition of extra-cellular H+, and by the addition of analogs of amiloride selective for inhibition of Na+/H+ exchange. The rate of recovery of pHi from acid load exhibited an ionic selectivity of Na+ greater than Li+ much greater than K+, and no recovery was observed in N-methyl-D-glucamine+. Tetrodotoxin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid had no effect on early pHi recovery. These data suggest that Na+/H+ exchange accounts primarily for the recovery of pHi in NG108-15 cells under our experimental conditions. Na+/H+ exchange in NG108-15 cells was accelerated by alpha 2-adrenergic receptors. Thus, (-)epinephrine, but not (+)epinephrine, elicited an intracellular alkalinization which was blocked by the alpha 2-adrenergic receptor selective antagonist yohimbine but not by the alpha 1-adrenergic receptor antagonist, prazosin, nor the beta-adrenergic antagonist, propranolol. Norepinephrine, clonidine, and the clonidine analog, UK-14304, also caused alkalinization of NG108-15 cells, whereas isoproterenol, a beta-adrenergic receptor agonist, and phenylephrine, a selective alpha 1-adrenergic receptor agonist, did not. Manipulations that blocked Na+/H+ exchange blocked the ability of alpha 2-adrenergic agonists to alkalinize the interior of NG108-15 cells without blocking the ability of these agonists to attenuate cAMP accumulation. These findings provide the first direct evidence of modulation of Na+/H+ exchange activity by a receptor linked to inhibition of adenylate cyclase and offer a possible mechanism whereby alpha 2-adrenergic receptors might influence cellular activity apart from changes in cyclic nucleotide metabolism.
 ...
PMID:Alpha 2-adrenergic receptors accelerate Na+/H+ exchange in neuroblastoma X glioma cells. 288 87

The generation of adenosine 3',5'-monophosphate (cyclic AMP) in response to catecholamines in the 2B subclone of RGC6 rat glioma cells previously exposed to norepinephrine and refractory to further norepinephrine addition is substantially increased by addition of inhibitors of RNA and protein synthesis. The time course of the effect of these inhibitors on cyclic AMP concentration suggests that rapid protein synthesis and turnover are involved in catecholamine refractoriness. Norepinephrine induction of cyclic nucleotide phosphodiesterase is demonstrable in RGC6 cells but not in the 2B subclone. Thus, catecholamine refractoriness cannot be attributed to induction of phosphodiesterase. This implies that induction of a protein or proteins, important in catecholamine refractoriness, affects the synthesis rather than the degradation of cyclic AMP.
 ...
PMID:Reversal of catecholamine refractoriness by inhibitors of RNA and protein synthesis. 437 82

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.
 ...
PMID:Cell culture as models for studying neural functions. 608 74

D-Ala2-Met5-enkephalin, morphine, and noradrenaline inhibit the adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells in a dose-dependent manner even after the enzyme has been preactivated by cholera toxin. Half-maximal inhibition and extent of inhibition are the same with native or cholera toxin-activated enzyme. The inhibition caused by opioids or noradrenaline are antagonized by naloxone or phentolamine, respectively. The effect of D-Ala2-Met5-enkephalin on cholera toxin-activated enzyme is immediate in onset and rapidly reversed by the addition of naloxone. Guanyl-5'-yl-imidodiphosphate stimulates basal activity but inhibits the enzyme activated by cholera toxin or prostaglandin E1. Stimulation occurs at a concentration of 100 microM or above, inhibition even at 0.1 microM. The inhibitory effect of the non-hydrolysable GTP analog is antagonized by GTP. Guanyl-5'-yl-methylenediphosphonate, another nonhydrolysable GTP analog, inhibits basal as well as cholera toxin-stimulated or prostaglandin E1-stimulated adenylate cyclase. Other guanine derivatives such as GDP, GMP, cyclic GMP, guanyl-5'-yl-phosphoric acid amide and guanosine have no effect under the same conditions. The results may be taken as a piece of evidence for two separate guanyl nucleotide-binding sites accompanying the adenylate cyclase in the hybrid cells and mediating, respectively, stimulation and inhibition of the enzyme by hormones.
 ...
PMID:Opioids, noradrenaline and GTP analogs inhibit cholera toxin activated adenylate cyclase in neuroblastoma x glioma hybrid cells. 625 56

Neuroblastoma x glioma hybrid cells NG 108-15 were chronically treated with opioid agonists and tested for their development of "tolerance" as evaluated by the loss of inhibitory activity of opioids upon cAMP-accumulation. Desensitization was dose-dependent and non-competitive and highly selective, since the activity of other, non-opioid inhibitory compounds, such as noradrenaline and carbachol, was not altered. Moreover, naloxone-induced "withdrawal signs" (revealed in the lack of change in cAMP) were lacking in preparations completely desensitized ("tolerant") towards opiate effects. These results reject the assumption of a common biochemical mechanism underlying both opiate tolerance and dependence and rather support the significance of an uncoupling of receptors from subsequent effector systems upon chronic opiate action.
 ...
PMID:Uncoupling of receptors is essential for opiate-induced desensitization (tolerance) in neuroblastoma x glioma hybrid cells NG 108-15. 631 90

Coelectrophoresis in two-dimensional gels of rat glial fibrillary acidic protein (GFA) and 32P-labeled whole cell extracts of rat C-6 glioma cells showed that the GFA migrated in close proximity to a previously noted phosphoprotein, 50K-6.1, of these cells. GFA electrophoresed as a 50K polypeptide with at least four charge variants, the most acidic of which coelectrophoresed with 50K-6.1. Exposure of the C-6 cultures to dibutyryl cyclic AMP (dbcAMP) for 48 h increased the relative abundance of the endogenous polypeptide associated with 50K-6.1 by threefold, consistent with the hypothesis that 50K-6.1 was GFA. Norepinephrine stimulated 50K-6.1 phosphorylation 3.2-fold in dbcAMP-induced cultures. Peptide mapping with V8 protease and subtilisin was used to test the hypothesis that GFA and 50K-6.1 were identical polypeptides. With V8 protease, the peptides generated from the [35S]methionine labeled putative GFA spot of the C-6 cells were indistinguishable from the stained bands derived from authentic GFA in mixed samples of the two proteins. Likewise, the 35S-labeled acidic satellite to the putative GFA spot also yielded a peptide map that matched that of the authentic GFA. 32P-labeled peptides derived from the 50K-6.1 protein were a subset of those from authentic GFA. With three subtilisin concentrations, 32P-labeled 50K-6.1 was degraded to peptides which were again a subset of the stained GFA peptides. A cytoskeletal fraction from 32P-labeled C-6 cells contained a 50K phosphoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glial fibrillary acidic protein: norepinephrine stimulated phosphorylation in intact C-6 glioma cells. 669 99

A new type of ligand for the study of P2-purinergic receptor subtypes was synthesized by combining and modifying conventional nucleoside chemistry with Fmoc solid phase peptide synthesis techniques. The tri- and tetra-aspartic acid derivatives of adenosine-5'-carboxylic acid (AdoCAsp3 and AdoCAsp4) were found to act as weak agonists at P2-purinergic receptors, (activated by ATP and UTP respectively) present on C6 glioma cells. AdoCAsp4 induced inositol 1,4,5-trisphosphate formation in the C6 cells with an EC50 of 73 microM. In addition, AdoCAsp4 was found to inhibit (IC50 approximately 80 microM) ATP-induced cytosolic [Ca2+] transients in these glioma cells. The glycine derivative, AdoCGly, increased evoked release of noradrenaline from mouse vas deferens slices, probably due to the blockade of presynaptic P2-autoreceptors. The possibility that aspartic, glutamic or gamma-carboxyglutamic residues may be used to replace phosphate groups on an ATP receptor ligand, opens up new ways in ligand design.
 ...
PMID:A new class of compounds, peptide derivatives of adenosine 5'-carboxylic acid, includes inhibitors of ATP receptor-mediated responses. 777 27


<< Previous 1 2 3 4 5 Next >>