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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of angiotensin II on the cytosolic free Ca2+ concentration was measured in single mouse neuroblastoma N1E-115 cells loaded with fura-2. Angiotensin II induced a transient concentration-dependent increase in Ca2+ and also increased the production of inositol polyphosphates. The Ca2+ increase did not require extracellular Ca2+ and was unaffected by pretreatment with pertussis toxin. These data suggest that angiotensin II increased Ca2+ by an inositol trisphosphate-mediated release of intracellular Ca2+ following activation of phospholipase C via a pertussis toxin-insensitive guanine nucleotide binding protein. Similar results were obtained with bradykinin. The angiotensin II- or bradykinin-induced increase in Ca2+ occurred after a concentration-dependent latent period. Low concentrations of agonist elicited a small increase in Ca2+ following a variable lag that sometimes exceeded 1 min, whereas at maximally effective angiotensin II concentrations a larger, more rapid increase in Ca2+ occurred without a measurable delay. In some cells, oscillatory increases in Ca2+ were induced by angiotensin II and bradykinin. Possible mechanisms to explain the concentration dependency of the latent period and the oscillatory nature of the increases of Ca2+ are discussed. These results indicate that the mouse neuroblastoma N1E-115 cell represents a useful model for studying the signal response transduction mechanisms regulating the effects of angiotensin II in neuronal cells.
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PMID:Angiotensin II effects on the cytosolic free Ca2+ concentration in N1E-115 neuroblastoma cells: kinetic properties of the Ca2+ transient measured in single fura-2-loaded cells. 229 17

The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor-stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK-N-SH was examined. Addition of either forskolin (or its water-soluble analog, L-85,8051), theophylline, isobutylmethylxanthine, or cholera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45-181% increase in cAMP concentration and a 27-70% inhibition of carbachol-stimulated inositol phosphate release. Through the use of digitonin-permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK-N-SH cells were exposed to prostaglandin E1, the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK-N-SH cells.
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PMID:Muscarinic receptor-stimulated phosphoinositide turnover in human SK-N-SH neuroblastoma cells: differential inhibition by agents that elevate cyclic AMP. 247 99

In neuroblastoma x glioma hybrid cells (NG 108-15) labelled with [32P]-trisodium phosphate, [3H]-inositol and [14C]-arachidonic acid, bradykinin stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) while it had no effect on the release of [14C]-arachidonic acid (AA). The effect on PIP2 was time- and dose-dependent with a maximal effect on [3H]-inositol- and [32P]-labelled cells after 10-30 s of stimulation with 10(-6) M bradykinin. However, the hydrolysis of [14C]-AA labelled PIP2 was delayed compared to the effect on [3H]- and [14C]-PIP2 and was not detectable until after 60 s of stimulation. Bradykinin stimulation resulted in an increased formation of [3H]-inositol phosphates (IP) and [32P]- and [14C]-phosphatidic acid (PA) but the time course for PA formation did not follow the time-course for PIP2 hydrolysis. A reduced labelling of [32P]- and [14C]-phosphatidylcholine was also found in stimulated cells suggesting that PA may derive from other sources than PIP2. In conclusion, our results indicate that bradykinin activates phospholipase C, but not phospholipase A2, in NG 108-15 cells.
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PMID:Bradykinin effects on phospholipid metabolism and its relation to arachidonic acid turnover in neuroblastoma x glioma hybrid cells (NG 108-15). 251 58

The relationship between muscarinic receptor-mediated inositol lipid hydrolysis and the generation of Ca2+ signals has been examined in human SK-N-SH neuroblastoma cells. The resting cytoplasmic calcium concentration [( Ca2+]i) as determined by fura-2 fluorescence measurements was 59 +/- 2 nM. Upon the addition of oxotremorine-M, there was a 4-fold increase in [Ca2+]i (293 +/- 18 nM), with half-maximal stimulation obtained at an agonist concentration of 8 microM, a value similar to that previously observed for the enhancement of phosphoinositide hydrolysis. Addition of partial muscarinic agonists for phosphoinositide turnover (bethanechol, oxo-2, and arecoline) elicited correspondingly smaller increases in [Ca2+]i than did oxotremorine-M. Inclusion of EGTA lowered the basal [Ca2+]i within 2 min and markedly reduced (greater than 60%) the magnitude of the agonist-induced rise in [Ca2+]i. Addition of muscarinic agonists to SK-N-SH cells that had been prelabeled with [3H]inositol led to the rapid (5-15 sec) release of inositol mono-, bis-, and triphosphates. When assayed under conditions similar to those employed for the fluorescence measurements, EGTA also inhibited both the basal and oxotremorine-M-stimulated release of inositol phosphates by 45-61%. Conversely, ionomycin both elevated [Ca2+]i and stimulated the release of inositol phosphates. The addition of Ca2+ (10 nM-2 microM) to digitonin-permeabilized cells directly stimulated the release of labeled inositol mono-, bis-, and trisphosphates by 3-4-fold with a half-maximal effect (EC50) observed at 145 nM free Ca2+ (Ca2+f). A further (6-fold) calcium-dependent increase in inositol phosphate release was obtained by inclusion of either guanosine-5-O-(3-thio)-trisphosphate (GTP gamma S) or oxotremorine-M. In the combined presence of agonist and GTP gamma S, a synergistic release of all three inositol phosphates occurred, with half-maximal stimulation observed at 35-40 nM Ca2+f, a value similar to the [Ca2+]i in quiescent cells. These results indicate (i) that the magnitude of the initial rise in [Ca2+]i is directly related to the production of phosphoinositide-derived second messenger molecules and (ii) that the phospholipase C-mediated breakdown of inositol lipids in SK-N-SH cells is particularly sensitive to regulation by physiologically relevant Ca2+ concentrations. It is concluded that, in SK-N-SH cells, either an elevation above or reduction below basal [Ca2+]i can modulate the extent of hydrolysis of inositol lipids and the subsequent generation of calcium signals.
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PMID:Muscarinic receptor regulation of cytoplasmic Ca2+ concentrations in human SK-N-SH neuroblastoma cells: Ca2+ requirements for phospholipase C activation. 253 57

The effects of mastoparan on phospholipase C-catalysed phosphoinositide hydrolysis were examined in [3H]inositol-labelled human neuroblastoma SH-SY5Y cells. [3H]Inositol phosphate formation in intact cells was not altered by 20 microM mastoparan. In contrast, [3H]inositol phosphate formation in electrically permeabilized cells stimulated with guanosine 5'-[gamma-thio]triphosphate and/or carbachol was inhibited by mastoparan with half-maximal effects at approx. 3 microM. The peptide was much less effective in inhibiting stimulatory effects of Ca2+. Similar but less potent inhibitory effects were observed with the cations, neomycin and spermine, indicating that direct interaction of mastoparan with polyphosphoinositides might account for its inhibitory effects on inositol phosphate formation.
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PMID:Phosphoinositide hydrolysis in permeabilized SH-SY5Y human neuroblastoma cells is inhibited by mastoparan. 254 Oct 20

1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from receptor activation of cells labelled with [3H]-inositol accumulate rapidly. The breakdown of both inositol monophosphate (InsP1) and inositol bisphosphate (InsP2) is sensitive to lithium with inhibition of the latter only observed at higher concentrations of this ion. 2. Use of the calcium indicator dye Fura 2 revealed that carbachol stimulates a biphasic increase in intracellular calcium. 3. Carbachol was able to stimulate both [3H]-inositol phosphate production and intracellular calcium levels with respective EC50 values of 15.9 +/- 1.0 microM and 10.7 +/- 3.2 microM, indicating that no amplification occurs between these steps in the signal transduction pathway. 4. Inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) released 45Ca2+ in a stereospecific and dose-related manner from intracellular stores of permeabilised cells. 5. These results suggest that this cell line may represent a useful model system to investigate receptor-mediated phosphoinositide metabolism and calcium homeostasis.
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PMID:Muscarinic receptors coupled to phosphoinositide hydrolysis and elevated cytosolic calcium in a human neuroblastoma cell line SK-N-SH. 255 60

Numerous studies have indicated that a modified proteinase K-resistant form of an endogenous brain protein, prion protein (PrP), is associated with scrapie infection in animals. This scrapie-associated PrP modification appears to occur posttranslationally in brain, but its molecular nature is not known. To learn about the normal PrP biosynthesis and whether it is altered by scrapie infection in vitro, we did metabolic labeling experiments with uninfected and scrapie-infected mouse neuroblastoma tissue culture cells. Pulse-chase labeling experiments indicated that, in both cell types, two major PrP precursors of 28 and 33 kilodaltons (kDa) were processed to mature 30- and 35- to 41-kDa forms. Endoglycosidase H, tunicamycin, and phospholipase treatments revealed that the 28- and 33-kDa precursors resulted from the addition of high-mannose glycans to a 25-kDa polypeptide containing a phosphatidylinositol moiety and that maturation of the precursors involved the conversion of the high-mannose glycans to hybrid or complex glycans. Treatments of the live cells with trypsin and phosphatidylinositol-specific phospholipase C indicated that the mature PrP species were expressed solely on the cell surface, where they were anchored by covalent linkage to phosphatidylinositol. Once on the cell surface, the major PrP forms had half-lives of 3 to 6 h. No differences in PrP biosynthesis were observed between the scrapie-infected versus uninfected neuroblastoma cells.
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PMID:Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells. 256 14

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).
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PMID:Heterologous desensitization of bradykinin-induced phosphatidylinositol response and Ca2+ mobilization by neurotensin in NG108-15 cells. 272 52

Islet-activating protein (IAP) was used to investigate the role of the guanosine triphosphate binding proteins Gi and/or Go in muscarinic acetylcholine receptor-mediated responses in neuroblastoma cells (clone N1E-115). Incubation of intact cells for 24 h with 20 ng/ml IAP resulted in inhibition of subsequent IAP catalyzed incorporation of [32P]ADP-ribose into a membrane protein doublet of molecular weight 40,000 (Gi alpha and Go alpha). IAP treatment fully blocked muscarinic receptor-mediated inhibition of cAMP accumulation. Incubation of intact cells with carbachol for 8 h resulted in the concentration dependent loss of membrane muscarinic receptor. Pretreatment of cells with IAP prior to carbachol exposure partially blocked the subsequent decrease in receptor number. Pretreatment of cells with IAP had no effect on the ability of carbachol to stimulate phosphoinositide hydrolysis in neuroblastoma cells. Thus, while the guanosine triphosphate binding proteins Gi and/or Go are involved in coupling the muscarinic receptor to some of the physiological responses in these cells, it is clear that activation of phospholipase C by the muscarinic receptor is a Gi/Go independent response.
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PMID:Modification of neuronal muscarinic receptor-mediated responses by islet-activating protein. 284 Oct 15

In neuroblastoma x glioma hybrid NG108-15 cells, bradykinin (BK) receptor stimulation leads to phosphoinositide hydrolysis, formation of inositol phosphates and mobilization of intracellular calcium. Treatment of the cells with 12-O-tetradecanoyl phorbol 13-acetate (TPA) suppressed the spike phase of increases in intracellular calcium concentration. In radioligand binding studies, TPA treatment did not interfere with [3H]BK specific binding to intact cells or to cell membranes. The ability of guanyl-5'-yl-imidodiphosphate to promote the conversion of the high affinity sites of the BK receptors into a low affinity sites was unaffected by TPA. TPA treatment showed the dose-dependent, noncompetitive inhibition of BK-stimulated formation of inositol trisphosphate. In the membrane preparations from TPA-treated cells, guanosine 5'-(3-O-thio)triphosphate-stimulated inositol trisphosphate formation was inhibited by 50%. These data indicate that TPA exerts its inhibitory action on BK responses at the sites of guanine nucleotide-binding protein or phospholipase C or both.
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PMID:Phorbol ester inhibits bradykinin-stimulated inositol trisphosphate formation and calcium mobilization in neuroblastoma x glioma hybrid NG108-15 cells. 287 10


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