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

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

The effect of lithium ion (Li+) on receptor-mediated synthesis of cyclic GMP, a putative second messenger, was examined using intact murine neuroblastoma cells (clone N1E-115). Lithium chloride potently inhibited cyclic GMP formation stimulated by the neuropeptides, neurotensin, angiotensin II and bradykinin in an identical concentration-dependent (IC50 s of around 12 mM), saturable and reversible manner. In the presence of veratridine, an alkaloid which by stimulating sodium channels can increase Li+ entry into the cells, Li+ inhibited neurotensin-stimulated cyclic GMP formation more potently (IC50 = 7 mM). No effect of Li+ was observed on phosphodiesterase (EC 3.1.4.17) activity. These results suggest that Li+ may interfere with the function of these receptors through its inhibitory effect at a common site in the pathway of receptor-mediated cyclic GMP formation.
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PMID:Lithium ions have a potent and selective inhibitory effect on cyclic GMP formation stimulated by neurotensin, angiotensin II and bradykinin. 301 10

Long-term preincubation at 37 degrees of mouse neuroblastoma cells (clones NS-20 and N1E-115) with soman, a potent and irreversible cholinesterase inhibitor, resulted in a significant decrease in the number of [3H]N-methylscopolamine binding sites and in the inhibition of carbamylcholine-induced cyclic GMP formation. The disappearance of surface muscarinic receptors and the desensitization of the receptor-mediated response seem to occur via accumulation of acetylcholine in the culture medium. The significance of these findings is discussed.
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PMID:Modulation of the number of muscarinic receptors in mouse neuroblastoma cells by soman. 302 49

The naturally occurring analogs of neurotensin-(8-13), xenopsin, [Lys8,Asn9]neurotensin-(8-13) (LANT-6) and neuromedin N stimulated the production of intracellular cyclic GMP in murine neuroblastoma clone N1E-115, an adrenergic neuronal cell type. The order of potency was neurotensin-(8-13) greater than neurotensin greater than xenopsin greater than neuromedin N greater than LANT-6. Furthermore, xenopsin, LANT-6 and neuromedin N each inhibited the specific binding of [3H]neurotensin to intact N1E-115 cells in a dose-related fashion. The order of affinity of the peptides for the neurotensin receptor was neurotensin-(8-13) greater than xenopsin greater than neurotensin greater than neuromedin N greater than LANT-6.
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PMID:LANT-6, xenopsin and neuromedin N stimulate cyclic GMP at neurotensin receptors. 302 8

We have found specific receptors for atrial natriuretic factor (ANF) in cultured neuroblastoma cells (N4TG1) of peripheral ganglionic origin. Scatchard analysis of the displacement binding revealed noninteracting, single-class binding sites with a KD of 1 X 10(-10) M and a density (Bmax) of 110,000-150,000 sites/cell. The cell-bound 125I-ANF was displaced by unlabeled ANF in a dose-dependent manner. Hormones unrelated to ANF such as angiotensins, adrenocorticotropic hormone, or arginine vasopressin were ineffective in displacing the cell-bound radioactivity. Using azidobenzoyl-125I-ANF as a photoaffinity ligand, an ANF receptor with an apparent Mr of 138,000 was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The addition of unlabeled ANF (1 microM) to the incubation medium completely abolished the labeling of this protein band, but atriopeptin I (1 microM) or angiotensins I, II, and III (each 1 microM) were not effective in inhibiting the affinity labeling. The treatment of the neuroblastoma cells with ANF stimulated intracellular cyclic GMP levels in a dose-dependent manner with an EC50 of 5 nM. ANF (1 X 10(-7) M) stimulated cyclic GMP accumulation in less than 5 min by 30-fold as compared to the controls.
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PMID:Identification of atrial natriuretic factor receptor of neuroblastoma N4TG1 cells: binding characteristics and photoaffinity labeling. 303 Dec 16

Neurotensin, some of its analogs, and neuromedin N were examined for comparison of their potencies at stimulating inositol phospholipid hydrolysis and cyclic GMP synthesis in intact murine neuroblastoma cells (clone N1E-115). Neurotensin(8-13) and acetylneurotensin(8-13) had the highest potencies for the stimulation of the hydrolysis of inositol phospholipid, which were about three times as potent as neurotensin (EC50 = 0.9 nM). On the other hand, fragments of the amino-terminal portion of neurotensin, such as neurotensin(1-6), neurotensin(1-8) and neurotensin(1-11), showed no ability to stimulate this hydrolysis. Neuromedin N, which is similar in structure to neurotensin(8-13) and which has been demonstrated to stimulate cyclic GMP formation [J.A. Gilbert and E. Richelson, Eur. J. Pharmac. 129, 379 (1986)], had EC50 values of 2.5 and 4.5 nM for release of [3H]inositol phosphates and stimulation of cyclic [3H]GMP respectively. A strong correlation was obtained between the EC50 values for neurotensin and several analogs in the stimulation of the release of inositol phosphates and the EC50 values for these peptides in the stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 cells under similar experimental conditions. Thus, these two different biochemical effects of neurotensin and its analogs appear to be mediated by the same receptor site, which may also have been the site of action of neuromedin N in these cells.
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PMID:Comparison of the stimulation of inositol phospholipid hydrolysis and of cyclic GMP formation by neurotensin, some of its analogs, and neuromedin N in neuroblastoma clone N1E-115. 303 99

The effects of phorbol 12-myristate 13-acetate (PMA) on carbamylcholine (CBC)-induced [3H]cyclic GMP formation in mouse neuroblastoma cells (clone N1E-115) were studied. PMA, but not 4 alpha-phorbol, suppressed muscarinic receptor-mediated cyclic GMP responses in a time-dependent and a concentration-dependent fashion with an IC50 of 68.8 +/- 20.2 nM. The inhibitory effects of PMA on CBC-induced cyclic GMP formation were of a mixed competitive and noncompetitive type, being characterized by a depression of maximal cyclic GMP response to CBC and a significant increase in its EC50. PMA also significantly reduced [3H]cyclic GMP formation induced by histamine, without affecting the responses elicited either by sodium azide or the calcium ionophore A23187. Although the inhibitory effects of PMA on CBC-induced cyclic GMP formation were not reversed by washing, these effects were significantly attenuated by H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], a protein kinase C inhibitor. PMA had no effect on binding of an antagonist ligand to muscarinic receptors, or on the binding characteristics of CBC to these receptors in intact cells. On the other hand, PMA competed for the specific binding of a labeled phorbol ester in intact cells with a potency similar to that of PMA in inhibiting muscarinic receptor-mediated [3H]cyclic GMP responses.
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PMID:Phorbol ester-induced inhibition of cyclic GMP formation mediated by muscarinic receptors in murine neuroblastoma cells. 303 12

Receptor-mediated cyclic GMP formation in N1E-115 murine neuroblastoma cells appears to involve oxidative metabolism of arachidonic acid. Evidence in support of this includes the blockade of this response by lipoxygenase inhibitors, e.g., eicosatetraynoic acid (ETYA) or other metabolic perturbants, e.g., methylene blue. It was recently discovered that the lipoxygenase products 15-hydroxyeicosatetraenoic (15-HETE) acid and 12-HETE, like ETYA, were inhibitors of M1 muscarinic receptor-mediated cyclic GMP formation. In the present report, the effects of monoHETEs are explored in more detail, particularly with regard to the function of the muscarinic receptor. Like 12-HETE and 15-HETE (IC50 = 13 and 11 microM, respectively), 5-HETE inhibited the cyclic GMP response to the muscarinic receptor (IC50 = 10 microM). All three of these monoHETEs were shown also to be inhibitors of the cyclic GMP responses to receptors stimulated by carbachol, histamine, thrombin, neurotensin, and bradykinin. 15-HETE was shown to inhibit the muscarinic receptor-mediated response in a complex manner (apparent noncompetitive and uncompetitive components; IC50 = 18 and 2 microM, respectively). 15-HETE did not inhibit either the M1 muscarinic receptor-stimulated release of [3H]inositol phosphates from cellular phospholipids or the M2 muscarinic receptor-mediated inhibition of hormone (prostaglandin E1)-induced AMP formation. It seemed possible that the monoHETEs could enter into biochemical pathways for arachidonate in N1E-115 cells. [3H]Arachidonate and the three [3H]-monoHETEs all rapidly labeled the membrane lipids of intact N1E-115 cells, with each [3H]eicosanoid producing a unique labeling profile. [3H]15-HETE labeling was noteworthy in that 85% of the label found in the phospholipids was in phosphatidylinositol (PI;t1/2 to steady state = 3 min). Exogenous 15-HETE inhibited the labeling of PI by [3H]arachidonate (IC50 = 28 microM) and elevated unesterified [3H]arachidonate levels. Thus, the mechanism of blockade of receptor-mediated cyclic GMP responses by monoHETEs is likely to be more complex than the simple inhibition of cytosolic mechanisms, e.g., generation of a putative second messenger by lipoxygenase, and may involve also alterations of membrane function accompanying the redistributions of esterified arachidonate.
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PMID:Blockade of receptor-mediated cyclic GMP formation by hydroxyeicosatetraenoic acid. 303 24

Adenosine 3',5'-cyclic monophosphate (cAMP) content of neurons is determined not only by the rate of synthesis but also by the rate of hydrolysis by cyclic nucleotide phosphodiesterases. Multiple forms of cyclic nucleotide phosphodiesterase exist in brain and other tissues, and these may be regulated by various hormones and neuromodulators. The present study examines this regulation in a cloned line of neuroblastoma cells (N18TG2). A biphasic Lineweaver-Burk plot of cAMP hydrolysis revealed two Kms approximating 5 and 25 microM. Lineweaver-Burk plots of cGMP hydrolysis were linear over a range of 1 microM to 1 mM and exhibited a Km of 37 microM. Neither cAMP nor cGMP competed for hydrolysis of the alternative cyclic nucleotide. No evidence for an allosteric activation of cAMP phosphodiesterase by cGMP was found. Calcium regulation of phosphodiesterase was not found in spite of preparation of the cell extract with several protease inhibitors, and addition of exogenous calmodulin. No effect of calmodulin antagonists (calmidazolium, W7, or trifluoperazine) was observed in vitro or in situ. Growth of the cells in the presence of 200 nM 3,5,3'-triiodothyronine (T3) resulted in an increased hydrolysis of cAMP but of cGMP. This increase was attributed to an increase in Vmax with no change in either high or low Km. This response was blocked by cycloheximide, suggesting that the thyroid hormone effect requires protein synthesis. The thyroid hormone response in neuroblastoma cells is compared with the results of other studies of thyroid hormone effects on phosphodiesterase in other tissues in vivo.
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PMID:Cyclic nucleotide phosphodiesterase isozymes in neuroblastoma cells. 303 96

The association of neurotensin to its receptor in differentiated neuroblastoma N1E115 cells led to a fast and transitory increase of the intracellular concentration in inositol triphosphate and inositol biphosphate, followed by a slower and more stable increase inositol monophosphate. The action of inositol 1,4,5-triphosphate on digitonin-permeabilized N1E115 cells resulted in a stimulation of cyclic GMP levels that mimicked that induced by neurotensin. Therefore, the cyclic GMP stimulation is probably a consequence of the initial inositol triphosphate formation triggered by neurotensin. Fluoroaluminate ions and pertussis toxin had the capacity to modulate positively and negatively, respectively, the formation of inositol triphosphate induced by neurotensin, indicating that GTP-binding proteins are involved in the regulation of inositol phosphate levels by neurotensin receptors.
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PMID:Stimulation of inositol phosphate production by neurotensin in neuroblastoma N1E115 cells: implication of GTP-binding proteins and relationship with the cyclic GMP response. 304 Sep 12


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