Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of short-and long-term ethanol exposure on bradykinin-stimulated hydrolysis of phosphatidylinositol 4.5-bisphosphate (PIP2) was investigated in neuroblastoma X glioma hybrid cells (NG 108-15). Acute exposure of 50-150 mM ethanol neither influenced the bradykinin-stimulated accumulation of [3H]-inositol phosphates (IP1, IP2, IP3) nor the hydrolysis of PIP2 in cells labelled with [3H]-inositol. Furthermore, ethanol (100 mM) added in the absence of agonist did not influence these parameters. However, in cells cultivated for 4 days in 100 mM ethanol, PIP2 hydrolysis and IP1, IP2 and IP3 formation after stimulation by 10(-6)-10(-5) M bradykinin was markedly inhibited while there was no effect on the basal levels or on the levels found after stimulation with low concentrations of bradykinin. The inhibitory effect of ethanol on IP accumulation became significant after 2-3 days of ethanol.
 ...
PMID:Ethanol effects on bradykinin-stimulated phosphoinositide hydrolysis in NG 108-15 neuroblastoma-glioma cells. 255 51

Two dynorphin-degrading cysteine proteases, I and II, were extracted with Triton X-100 from neuroblastoma cell membrane, isolated from accompanying dynorphin-degrading trypsin-like enzyme by affinity chromatography on columns of soybean trypsin inhibitor-immobilized Sepharose and p-mercuribenzoate-Sepharose, and separated by ion-exchange chromatography on diethylaminoethyl (DEAE)-cellulose and TSK gel DEAE-5PW columns. Cysteine protease II was purified further by hydroxyapatite chromatography and gel filtration. The molecular weights of cysteine proteases I and II were estimated to be 100,000 and 70,000, respectively, by gel filtration. Both of the enzymes, were inhibited by p-chloromercuribenzoate, N-ethylmaleimide, and high-molecular-weight kininogen, but not or only slightly inhibited by diisopropylphosphorofluoridate, antipain, leupeptin, E-64, calpain inhibitor, and phosphoramidon. Cysteine protease I cleaved dynorphin(1-17) at the Arg6-Arg7 bond with the optimum pH of 8.0, whereas II cleaved dynorphin(1-17) at the Lys11-Leu12 bond and the Leu12-Lys13 bond with the optimum pH values of 8.0 and 6.0, respectively. These bonds corresponded to those that had been proposed as the initial sites of degradation by neuroblastoma cell membrane. Cysteine protease I was further found to show strict specificity toward the Arg-Arg doublet, when susceptibilities of various peptides containing paired basic residues were examined as substrates for the enzyme.
 ...
PMID:Characterization of cysteine proteases functioning in degradation of dynorphin in neuroblastoma cells: evidence for the presence of a novel enzyme with strict specificity toward paired basic residues. 256 12

Neurotensin, bradykinin and somatostatin inhibited in a time- and concentration-dependent manner prostaglandin E1- or forskolin-stimulated cAMP production in neuroblastoma N1E115 cells. Cell treatment with 1 microgram/ml pertussis toxin for 6 hours reversed the inhibition elicited by peptides after short incubation periods (less than or equal to 1 min) but, in contrast, had no effect after longer incubation periods (greater than or equal to 3 min). Fluoroaluminate also inhibited prostaglandin E1-stimulated cAMP production in N1E115 cells, and this effect was not reversed by pertussis toxin. The 6 hour treatment with pertussis toxin was shown to be sufficient to ADP ribosylate virtually all of the 41 kD protein substrate corresponding to the alpha subunit of Gi. Protein kinase C activation with phorbol ester did not inhibit basal or stimulated cAMP production. Our data point to the existence of both pertussis toxin sensitive and insensitive mechanisms of neuropeptide-mediated inhibition of cAMP formation in N1E115 cells. The toxin insensitive response is not mediated by protein kinase C. The possibility is discussed that it results from the activation of a pertussis toxin insensitive G protein.
 ...
PMID:Neurotensin, bradykinin and somatostatin inhibit cAMP production in neuroblastoma N1E115 cells via both pertussis toxin sensitive and insensitive mechanisms. 256 13

The addition of bradykinin to 32Pi-labeled neuroblastoma X glioma hybrid NG108-15 cells caused a substantial loss of radioactivity from phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2). The bradykinin-induced hydrolysis of PI-4,5-P2 was almost equally observed even when extracellular Ca2+ was depleted with EGTA (100 microns). On the other hand, high K+ depolarization of the cells, which allows Ca2+ influx through voltage-dependent Ca2+ channels, failed to induce any significant decrease in the radioactivity of PI-4,5-P2. These data indicate that the bradykinin-stimulated PI-4,5-P2 hydrolysis in NG108-15 cells is independent of extracellular Ca2+ and also that PI-4,5-P2 hydrolysis is not stimulated by an elevation of intracellular Ca2+ concentration.
 ...
PMID:Evidence for a Ca2+-independent hydrolysis of phosphatidylinositol 4,5-bisphosphate in neuron-like cell line NG108-15 cells. 258 Jul 37

Accumulation of inositol phosphates in NG108-15 neuroblastoma x glioma hybrid cells, pre-labeled for 24h to equilibrium, was stimulated by bradykinin, guanosine 5'-O-(3-thiotriphosphate) and the diacylglycerol kinase inhibitor R59022. Only the stimulation by bradykinin was inhibited by the bradykinin receptor antagonist [D-Arg0, Hyp3, Phe7, Thi5,8] bradykinin. Neither bradykinin nor R059022 increased the labeling of the inositol phospholipids. The sulfhydryl-alkylating reagent N-ethylmaleimide at 100 microM essentially abolished the stimulation caused by all three agents, possibly by preventing the binding of GTP to a guanine nucleotide-binding regulatory protein of as yet unknown size.
 ...
PMID:Effects of bradykinin, GTP gamma S, R59022 and N-ethylmaleimide on inositol phosphate production in NG108-15 cells. 268 44

The heterologous desensitization of the bradykinin (BK)-induced increase in intracellular Ca2+ concentration ([Ca2+]i) by neurotensin was studied in neuroblastoma x glioma hybrid NG108-15 cells. The addition of neurotensin to the cells resulted in an increase in [Ca2+]i and an increase in the formation of inositol phosphates in Ca2+-free medium. Pretreatment of the cells with neurotensin resulted in 43% decrease in the BK-induced increase of [Ca2+]i. The increase in [Ca2+]i induced by ionomycin, which causes Ca2+ release from the intracellular pool, was not decreased by pretreatment with neurotensin. This indicates that the inhibitory effect of neurotensin on the BK-induced increase of [Ca2+]i was not due to depletion of the intracellular Ca2+ pool. Pretreatment with neurotensin also caused a 47% decrease in the BK-induced formation of inositol trisphosphates (IP3). This decrease was not due to depletion of phosphatidylinositol bisphosphates. Neurotensin did not inhibit [3H]BK binding to cell membranes. These results show that neurotensin desensitizes the BK responses of NG108-15 cells, heterologously, perhaps by changes in phospholipase C and/or guanine nucleotide-binding protein (G-protein).
 ...
PMID:Heterologous desensitization of bradykinin-induced phosphatidylinositol response and Ca2+ mobilization by neurotensin in NG108-15 cells. 272 52

Changing extracellular pH (pHo) from 7.4 to 6.1 increased [3H]inositol bis- and trisphosphates approximately 10- and 5-fold, respectively, in 15 s in human fibroblasts. [3H]Inositol phosphate increased less rapidly than the polyphosphates. Bradykinin similarly increased [3H]inositol phosphates. Shifting pHo from 7.4 to 6.0 evoked a large spike in cytosolic free Ca2+ [( Ca2+]i) which was primarily caused by the release of stored Ca2+. Changing pHo from 7.4 to 6.0 decreased cytoplasmic pH to approximately 7.0. Moderate decreases in intracellular pH had no effect on [Ca2+]i or 45Ca2+ efflux. Decreasing pHo strikingly increased 45Ca2+ efflux and decreased total cell Ca2+ similarly to bradykinin. Changing pHo from 7.4 to approximately 6.4 produced half-maximal effects on [Ca2+]i, 45Ca2+ efflux, and total Ca2+. Cycling pHo between 7.4 and 6.0 produced repetitive decreases and increases in total Ca2+. Bradykinin released the Ca2+ which was reaccumulated after an acid pulse indicating that Ca2+ had returned to the hormone-sensitive pool. Decreasing pHo also released stored Ca2+ from coronary endothelial, neuroblastoma, and umbilical artery muscle cells, but not from rat aortic smooth muscle or human epidermoid carcinoma (A431) cells. We suggest that lowering pHo stimulates a phosphoinositidase-coupled receptor by protonating a functional group with a pKa near 6.5.
 ...
PMID:Lowering extracellular pH evokes inositol polyphosphate formation and calcium mobilization. 272 98

Bradykinin (BK)-induced production of 1,2-diacylglycerol (1,2-DG) and translocation of protein kinases C (PKCs) were examined in neuroblastoma-derived hybrid NCB-20 cells. Mass analysis of 1,2-DG exhibited a biphasic increase by 1 microM BK stimulation: the first transient phase and the second broad sustained phase. Among three subspecies of PKC expressed in these cells, types II and III were observed to translocate from cytosol to membrane in response to BK as well as PBt2 by Western blotting analysis. Type II translocated more rapidly and distinctly than type III. However, after treatment with quin 2/AM, the second phase of 1,2-DG formation completely disappeared and PKCs translocation by BK or PBt2 was completely abolished. BK-induced IP3 (1,4,5) formation was temporally consistent with the first transient phase of 1,2-DG formation. These findings suggest that PKCs translocation by BK stimulation is caused by 1,2-DG produced not only via phosphoinositide metabolism, but via other phospholipid breakdown which is Ca2+-dependent.
 ...
PMID:Bradykinin-induced translocation of protein kinases C in neuroblastoma NCB-20 cell: dependence on 1,2-diacylglycerol content and free calcium. 276 33

The relative capacities of muscarinic cholinergic receptor (MR) and bradykinin (BK)-receptor activation to increase phosphoinositide hydrolysis and to increase cytosolic Ca2+ were compared in NG108-15 neuroblastoma x glioma and 1321N1 human astrocytoma cells. In 1321N1 cells, the muscarinic cholinergic agonist carbachol and BK each stimulated a concentration-dependent accumulation of inositol phosphates (K0.5 approximately 10 microM and approximately 10 nM respectively) and a rapid increase in cytosolic Ca2+ as determined by quin2 fluorescence. In NG108-15 cells, BK alone stimulated a pertussis-toxin-insensitive accumulation of inositol phosphates (K0.5 approximately 10 nM) under conditions in which pertussis toxin completely inhibited MR-mediated inhibition of adenylate cyclase. BK also stimulated a rapid increase in cytosolic Ca2+ in NG108-15 cells. In contrast, no MR-mediated increase in phosphoinositide hydrolysis or change in cytosolic Ca2+ concentration was observed in NG108-15 cells. These results support the idea that MR selectively interact with either the cyclic AMP or the inositol phosphate second-messenger systems.
 ...
PMID:Evidence that muscarinic cholinergic receptors selectively interact with either the cyclic AMP or the inositol phosphate second-messenger response systems. 282 38

Murine neuroblastoma clone N1E-115 possesses receptors that specifically bind the tridecapeptide neurotensin, mediate the formation of intracellular cyclic GMP, and stimulate inositol phospholipid hydrolysis. These cells also rapidly degrade neurotensin in a sequential fashion. We studied the effect of prolonged exposure of cells to neurotensin on subsequent neurotensin receptor-mediated intracellular cyclic GMP formation under conditions that prevented degradation of this peptide [J. A. Gilbert and E. Richelson, Soc. Neurosci. Abstr. 12, 762 (1986)]. Neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115 was decreased following prolonged exposure of intact cells to nondegraded neurotensin. The time course of this desensitization was very rapid; the maximal effect on cyclic GMP production (reduction to 10-30% of control values) occurred within 5 min of exposure of intact cells to neurotensin. This desensitization was homologous, as cells desensitized by neurotensin demonstrated no decrease in their cyclic GMP response to angiotensin II (1 microM) or bradykinin (10 nM). Neurotensin preincubation with intact N1E-115 cells for increasing lengths of time caused time-dependent shifts to the right of the dose-response curve and reductions in the maximum cyclic GMP response. Desensitization was reversible, but resensitization was a slower process than desensitization: full recovery of cyclic GMP production required incubation of the desensitized cells for at least 10 min at 37 degrees. From binding studies with [3H]neurotensin, we found that both the apparent equilibrium dissociation constant, KD, and the maximum number of receptor sites, Bmax, for this radioligand were decreased significantly (P less than 0.05) for completely desensitized cells from those values for control cells. These data suggest that desensitization of the neurotensin receptor involved an uncoupling of the pathway of events connecting receptor activation to intracellular cyclic GMP formation; complete desensitization involved both the apparent loss of neurotensin receptors on the cellular surface and the increase in affinity of the remaining receptors for the agonist. This decrease in Bmax is more likely to be a result of intracellular sequestration of recyclable NT receptors than of true down-regulation due to the rapid resensitization seen for the NT-mediated biological response.
 ...
PMID:Desensitization of neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115. 284 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>