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

Little is known about the factors which regulate the growth and development of the mammalian brain. Although proliferation of neuronal cells ceases relatively early in development, certain types of glial cells proliferate and differentiate mainly perinatally. In the perinatal period, the ability of acetylcholine to stimulate phosphoinositide (PI) hydrolysis in brain reaches peak levels, and indeed the stable acetylcholine analogue carbachol can stimulate PI hydrolysis of primary neonatal astroglial cells. As PI hydrolysis is thought to be important in the regulation of cell proliferation, we investigated whether cellular DNA synthesis can be induced by carbachol. Our results show that carbachol stimulates DNA synthesis via muscarinic acetylcholine receptors (mAChRs), in primary astrocytes derived from perinatal rat brain, in an age-dependent fashion. Carbachol is also mitogenic in certain brain-derived astrocytoma and neuroblastoma cell lines, as well as in chinese hamster ovary (CHO) cells expressing recombinant muscarinic receptors. DNA synthesis is strongly activated by carbachol in those brain-derived cell lines and transfected CHO cells that express mAChR subtypes which activate PI hydrolysis efficiently, and poorly activated in cells expressing mAChR subtypes which only weakly activate PI hydrolysis. These results strongly support a role for acetylcholine in regulating astroglial cell growth in the developing brain, and indicate that the specificity of acetylcholine-induced cell proliferation may be determined by the expression of those mAChR subtypes which activate PI hydrolysis.
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PMID:Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. 273 37

Hormonal regulation of Mg2+ influx was examined in the neuroblastoma X glioma hybrid cell line NG108-15 and the skeletal muscle cell line G8 using 28Mg2+. Both cell lines express multiple classes of hormone receptors; in addition, G8 cells can be induced to differentiate from a single myoblast-like cell into fused myotube-like cells. In NG108-15 cells, 2-Cl-adenosine, an adenosine receptor agonist, stimulated Mg2+ influx by about 60%. This effect was not mimicked by norepinephrine or PGE1, agonists at alpha 2-adrenergic and prostaglandin receptors which NG108-15 cells also express. Carbachol, acting through a muscarinic receptor, gave minimal and variable stimulation of Mg2+ influx. The effect of 2-Cl-adenosine was not blocked by theophylline, an adenosine receptor antagonist, and was not mimicked by adenosine analogs selective for either A1 or A2 adenosine receptors, suggesting that a nonclassical adenosine receptor mediates the effect on Mg2+ influx. Theophylline slightly stimulated Mg2+ influx as did the permeable cyclic AMP analog, 8-Br-cyclic AMP. These results indicate that cyclic AMP may influence Mg2+ influx in NG108-15 cells unlike previous results in murine S49 lymphoma cells [Maguire and Erdos, J. biol. Chem. 255: 1030-1035, 1980] where receptor modulation of Mg2+ influx was independent of cyclic AMP. In G8 cells, the nicotinic cholinergic receptor agonist carbachol stimulated Mg2+ influx at the myoblast cell stage but had no effect on Mg2+ influx after cells had formed myotubes. The beta-adrenergic agonist isoproterenol had the opposite effect, stimulating Mg2+ influx in the myotube stage but not in the myoblast stage. Taken together, these results demonstrate that only a subset of receptors expressed by a cell may be coupled to Mg2+ influx, that the regulation of Mg2+ influx differs from cell type to cell type, and finally, that modulation of Mg2+ influx by hormone receptors may change with differentiation.
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PMID:Hormonal regulation of magnesium uptake: differential coupling of membrane receptors to magnesium uptake. 282 11

The role of intracellular free Ca2+ in muscarinic-receptor linked depolarization of SH-SY5Y neuroblastoma cells has been determined by using the bisoxonol membrane potential probe DiBaC4-(3) and intracellular Ca2+ indicator fura-2 respectively. Carbachol and the Ca2+ ionophore, ionomycin, at concentrations which caused similar rises in intracellular Ca2+ increased the bisoxonol fluorescence (depolarization) to the same extent. The membrane potential responses, but not the changes in intracellular Ca2+, were dependent on extracellular Na+. Ionomycin depletion of intracellular Ca2+ with EGTA and ionomycin or loading the cells with a Ca2+ buffer, BAPTA, reduced the carbachol-induced depolarization. The results suggest that a rise in intracellular Ca2+ may cause depolarization through an increase in the Na+ permeability.
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PMID:Depolarization of human neuroblastoma cells as a result of muscarinic receptor-induced rise in cytosolic Ca2+. 291 16

Murine neuroblastoma cells (clone N1E-115) possess two subtypes of the muscarinic receptor each of which separately mediates a cyclic nucleotide response. The formation of cyclic GMP is postulated to involve a low affinity agonist-receptor conformation, whereas the reduction of prostaglandin E1-stimulated cyclic AMP formation appears to involve a high affinity conformation. Further evidence supporting this hypothesis was obtained in experiments measuring the equilibrium dissociation constants for the full agonist carbachol by the method of partial receptor inactivation. Quinuclidinyl benzilate (QNB) was employed to occlude muscarinic receptors; measurements with [3H] QNB ensured that the amount of QNB appearing in the assay after washout had only a minimal effect on the determination of the equilibrium dissociation constants. Carbachol mediated cyclic GMP formation with an equilibrium dissociation constant (KD) of 325 microM and cyclic AMP reductions with a KD value of 13 microM. These KD values are similar to but somewhat higher than those determined by direct binding at 15 degrees, and they are strong evidence in support of the view that a low affinity conformation mediates cyclic GMP formation, whereas a high affinity conformation mediates cyclic AMP reductions.
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PMID:Muscarinic responses and binding in a murine neuroblastoma clone (N1E-115): cyclic GMP formation is mediated by a low affinity agonist-receptor conformation and cyclic AMP reduction is mediated by a high affinity agonist-receptor conformation. 301 77

Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane.
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PMID:Activation of dopamine receptors does not affect phosphoinositide turnover in NCB-20 cells. 303 93

Tyrosine hydroxylase (TH) activity is increased two- to threefold in neuroblastoma cell line NBP2 maintained in culture for 48 h in the presence of either the inhibitor of cyclic AMP-phosphodiesterase (PDE), 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724), or the activator of adenylate cyclase, prostaglandin E1 (PGE1). Cyclic AMP levels are elevated 70-80% and 30-40% throughout the 48-h treatment with RO 20-1724 and PGE1, respectively. Carbachol does not affect either basal TH activity or cyclic AMP levels in the cells. However, the cholinergic agonist delays the induction of TH elicited by either RO 20-1724 or PGE1. This delay is prevented by atropine. The elevation in cyclic AMP levels elicited by either RO 20-1724 or PGE1 is blocked for 1 h or 15 min, respectively, after treatment with carbachol. Cyclic AMP levels then begin to rise until they reach those levels observed in the presence of RO 20-1724 or PGE1 alone by 12 h or 1 h of treatment, respectively. Time course studies demonstrate that this transient inhibition of the elevation of cyclic AMP is associated with a 48-h delay in the induction of TH elicited by either RO 20-1724 or PGE1. In contrast, the induction elicited by 8-bromo cyclic AMP is unaffected by carbachol. A depolarizing concentration (56 mM) of KCl produces a 24-h delay in the induction of TH elicited by RO 20-1724, without affecting the concomitant elevation of cyclic AMP produced by the PDE inhibitor. Furthermore, 56 mM-KCl inhibits the induction of TH elicited by 8-bromo cyclic AMP. It thus appears that carbachol delays the induction of TH by transiently inhibiting the elevation of cyclic AMP, whereas potassium depolarization delays the induction of TH by inhibiting a process with a site of action that is distal to the elevation of cyclic AMP.
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PMID:Effect of carbachol and 56 mm-potassium chloride on the cyclic AMP-mediated induction of tyrosine hydroxylase in neuroblastoma cells in culture. 610 63

The coupling of m5 muscarinic acetylcholine receptors to the generation and release of nitric oxide (NO) was investigated. Chinese hamster ovary cells, which stably express m5 receptors, were transiently transfected with the gene encoding neuronal NO synthase and used as a model system. Increased generation of NO upon stimulation of cells by muscarinic agonists was detected by an increase in cyclic GMP in admixed mouse neuroblastoma N1E-115 cells or more directly by measuring the conversion of L-arginine into L-citrulline. Carbachol increased cyclic GMP formation in the mixture of cells in a time- and concentration-dependent manner, with a half-maximal response occurring in the nanomolar range. This response was significantly attenuated by scavengers of NO or inhibitors of NO synthase. This high potency of carbachol was also observed in measurements of L-citrulline formation. A series of muscarinic agonists were as efficacious as carbachol in stimulating NO synthase, whereas McN-A-343 and pilocarpine were partial agonists in this regard. Evidence for an exceptionally high efficiency of coupling of m5 receptors to this response and its possible implication in the interaction between cholinergic and dopaminergic neurotransmission is discussed.
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PMID:Efficient coupling of m5 muscarinic acetylcholine receptors to activation of nitric oxide synthase. 750 88

1. Muscarinic and bradykinin receptor-mediated Ins(1,4,5)P3 accumulation, Ca2+ mobilization and Ca2+ entry have been examined in human SH-SY5Y neuroblastoma cells. This has allowed both direct comparison of signalling events by two receptor types potentially linked to the same transduction pathway and an investigation of the interactions between the components of this pathway. 2. Stimulation of muscarinic receptors with carbachol produced biphasic accumulations of Ins(1,4,5)P3 consisting of a rapid peak followed by a lower sustained phase. Both phases were dose-dependent but the potency of elevation at peak was significantly less than that of the sustained phase. Bradykinin also dose-dependently stimulated Ins(1,4,5)P3 accumulation but responses were smaller and not sustained. 3. Lowering of [Ca2+]e reduced basal Ins(1,4,5)P3 levels. Peak Ins(1,4,5)P3 elevation in response to carbachol and bradykinin were lowered by an amount approximating this reduction over the entire dose-response curves. Sustained Ins(1,4,5)P3 elevation in response to carbachol showed a more marked absolute reduction. Agonist potencies were unaffected by lowering [Ca2+]e. Thus, a consistent but small amount of PLC activity during rapid activation appears to be sensitive to lowered [Ca2+]e, whilst activity during sustained stimulation is greatly facilitated by external Ca2+, probably through Ca2+ entry. 4. The temporal- and dose-dependency of carbachol-mediated Ins(1,4,5)P3 accumulations were unaffected by loading cells with fura-2, thus allowing direct comparison of Ins(1,4,5)P3 and [Ca2+]i changes monitored by fura-2. 5. Changes in [Ca2+]i by both agonists revealed temporal patterns that were similar to Ins(1,4,5)P3 accumulations. Only carbachol stimulated a marked sustained [Ca2+]i signal and this was fully dependent on external Ca2+. 6. All agonist-mediated [Ca2+]i elevations occurred with significantly greater potency than that of the respective Ins(1,4,5)P3 accumulations. Further examination of peak elevations in response to carbachol indicated that this was independent of Ca2+ entry. Thus, a major site for amplification of the potency of rapid agonist-mediated responses lies at the level of the Ins(1,4,5)P3 receptor. 7. The transient nature of Ins(1,4,5)P3 and [Ca2+]i peaks followed by either lower but sustained levels with carbachol or a return to basal levels with bradykinin suggests rapid but partial desensitization of the muscarinic receptor and complete desensitization of the bradykinin receptor. This indicates receptor-specific desensitization. Further analysis of this was provided by detecting accumulations of [3H]-inositol phosphates ([3H]-InsPs) in Li(+)-blocked, myo-[3H]-inositol labelled cells. Carbachol produced a rapid accumulation over the first minute, followed by a slower linear accumulation for at least 29 min. At this point accumulations were dose-related with a potency similar to that of sustained Ins(1,4,5)P3 accumulation.However, bradykinin produced a minor accumulation of [3H]-InsPs, maximal by 1 min. Thus,analysis of PLC activation by measurement of [3H]-InsPs over relatively long time frames will indicate the ability of agonists for predominantly sustained PLC activation, potentially driven by a partially desensitized receptor, as opposed to rapid activation by a fully sensitized receptor.8. These data provide quantitative comparisons between and within components of the receptor mediated phosphoinositide and Ca2+ signalling pathway, provide mechanistic insights into regulation of these components and characterize a model system in which heterologous interaction between two receptors linked to the same transduction pathway may be examined.
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PMID:Quantitative comparisons of muscarinic and bradykinin receptor-mediated Ins (1,4,5)P3 accumulation and Ca2+ signalling in human neuroblastoma cells. 762 Jul 2

Activation of the G-protein-coupled muscarinic (M3) receptor in human neuroblastoma SH-SY5Y cells is known to lead to phosphoinositol hydrolysis and noradrenaline release. In this study, the effect of carbachol on tyrosine phosphorylation and mitogen-activated protein (MAP) kinase activity in SH-SY5Y cells was examined. Carbachol concentration-dependently induced tyrosine phosphorylation of several proteins, including one of 42 kDa. This tyrosine-phosphorylated 42 kDa protein co-eluted from a Mono Q anion-exchange column with MAP kinase activity and with immunologically detected MAP kinase. Stimulation of tyrosine phosphorylation and activation of MAP kinase were also observed after incubation of cells with phorbol 12-myristate 13-acetate (PMA) and epidermal growth factor (EGF). Down-regulation or inhibition of protein kinase C (PKC) abolished the stimulatory effects of both carbachol and PMA on MAP kinase activity, whereas EGF-stimulated MAP kinase activity remained unaffected. Thus carbachol acting through the muscarinic (M3) receptor PKC-dependently induced tyrosine phosphorylation and activation of a 42 kDa MAP kinase in SH-SY5Y cells, whereas EGF-induced MAP kinase activation occurred independently of PKC.
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PMID:Stimulation of tyrosine phosphorylation and mitogen-activated-protein (MAP) kinase activity in human SH-SY5Y neuroblastoma cells by carbachol. 769 May 47

Measurement of the intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded single cells of the human neuroblastoma line SH-SY5Y indicated coexpression of muscarinic and bradykinin receptors linked to activation of phosphoinositidase C (PIC). Both agonists elevated [Ca2+]i and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] levels in populations of adherent cells, although in cells used directly upon attainment of confluence the responses to carbachol were greater than those to bradykinin and displayed additional sustained components. This model system was used to examine heterologous interactions when a second PIC-linked agonist was added 100-300 sec after but in the continued presence of the first. Maximal (1 mM) carbachol concentrations abolished the elevation of [Ca2+]i produced by bradykinin but the muscarinic antagonist atropine (10 microM) restored the response, provided that extracellular Ca2+ was present throughout the experiment or was added before bradykinin. Carbachol also abolished bradykinin-mediated Ins(1,4,5)P3 elevation. In contrast, bradykinin did not influence [Ca2+]i or Ins(1,4,5)P3 responses to carbachol in the presence of extracellular Ca2+. In cells maintained at confluence for 2 weeks, the rapid peak elevations of [Ca2+]i and Ins(1,4,5)P3 levels induced by carbachol and bradykinin were approximately equivalent in magnitude. In these cells carbachol again abolished bradykinin-mediated elevation of [Ca2+]i but only attenuated, rather than abolished, the elevation of Ins(1,4,5)P3 levels. The [Ca2+]i and Ins(1,4,5)P3 responses to bradykinin were fully restored 100 sec after atropine only in the presence of extracellular Ca2+. Thus, depletion of an intracellular Ins(1,4,5)P3-sensitive Ca2+ store may underlie the ability of carbachol to produce not only heterologous desensitization of the [Ca2+]i elevation induced by bradykinin but also that of the Ins(1,4,5)P3 response. This suggests a feed-forward activation of PIC by Ca2+ released from Ins(1,4,5)P3-sensitive stores. Furthermore, studies in which Ins(1,4,5)P3-sensitive stores were depleted with thapsigargin and cells were challenged in the presence or absence of extracellular Ca2+ indicated that Ca2+, irrespective of its origin (intra- or extracellular), potentiated the Ins(1,4,5)P3 response to bradykinin alone. In cells maintained at confluence for 2 weeks, bradykinin was again unable to influence either [Ca2+]i or Ins(1,4,5)P3 responses to carbachol in the presence of Ca2+. This lack of heterologous desensitization may be due to the rapid, full, homologous desensitization of bradykinin receptors, compared with an incomplete homologous desensitization of muscarinic receptors.
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PMID:Heterologous desensitization of both phosphoinositide and Ca2+ signaling in SH-SY5Y neuroblastoma cells: a role for intracellular Ca2+ store depletion? 770 Feb 49


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