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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 neurotensin receptors that mediate cyclic GMP synthesis. Because of the hypothesized relationship between phospholipid metabolism, intracellular Ca2+, and cyclic GMP synthesis, we determined with these cells the effects of neurotensin on 32P labeling of phospholipids, release of inositol phosphates, and intracellular Ca2+ (as determined with the use of Quin-2, a fluorescent probe sensitive to free Ca2+ levels). Neurotensin stimulated incorporation of 32P into phospholipids, especially phosphatidylinositol and phosphatidate. Neurotensin also stimulated the release of [3H]inositol phosphates with an EC50 of about 1 nM. Mean basal Ca2+ concentration in these cells was 134 nM and this level was increased in a rapid and dose-dependent manner by neurotensin, with an EC50 of 4 nM. Since the EC50 for neurotensin in stimulating cyclic GMP synthesis is 1.5 nM and the KD for binding of [3H]neurotensin at 0 degrees C is 11 nM, all these different effects appear to be shared proximal consequences of neurotensin receptor activation.
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PMID:Neurotensin stimulates inositol phospholipid metabolism and calcium mobilization in murine neuroblastoma clone N1E-115. 301 65

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

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

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

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

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

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

Membranes prepared from mammalian brain or intestine contain two types of specific binding sites for neurotensin that differ by their affinity and by their sensitivity to sodium ions, GTP, and the antihistamine drug levocabastine. Only the high affinity sites are present in cell cultures and in soluble extracts of CHAPS-treated membranes. These sites represent functional neurotensin receptors coupled to GTP-binding proteins that regulate intracellular levels of cAMP, cGMP and inositol phosphates in neuroblastoma N1E115 cells. The molecular weight of neurotensin receptors in cells and membrane preparations of various origin is about 110,000.
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PMID:Functional properties and molecular structure of central and peripheral neurotensin receptors. 304 Sep 76

The mechanisms by which neurotensin (NT) was inactivated by differentiated neuroblastoma and HT29 cells were characterized. In both cell lines, the sites of primary cleavages of NT were Pro7-Arg8, Arg8-Arg9 and Pro10-Tyr11 bonds. The cleavage at the Pro7-Arg8 bond was totally inhibited by N-benzyloxycarbonyl-Prolyl-Prolinal and therefore resulted from the action of proline endopeptidase. This peptidase also contributed in a major way to the cleavage at the Pro10-Tyr11 bond. However the latter breakdown was partly due to an NT-degrading neutral metallopeptidase. Finally, we demonstrated the involvement of a recently purified rat brain soluble metalloendopeptidase at the Arg8-Arg9 site by the use of its specific inhibitor N-[1(R,S)-carboxy-2-Phenylethyl]-alanylalanylphenylalanine-p-amino benzoate. The secondary processing of NT degradation products revealed differences between HT29 and N1E115 cells. Angiotensin converting enzyme was shown to degrade NT1-10 and NT1-7 in N1E115 cells but was not detected in HT29 cells. A post-proline dipeptidyl aminopeptidase activity converted NT9-13 into NT11-13 in HT29 cells but not in N1E115 cells. Finally bestatin-sensitive aminopeptidases rapidly broke down NT11-13 to Tyr in both cell lines. Models for the inactivation of NT in HT29 and N1E115 cells are proposed and compared to that previously described for purified rat brain synaptic membranes.
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PMID:Catabolism of neurotensin by neural (neuroblastoma clone N1E115) and extraneural (HT29) cell lines. 356 17

Murine neuroblastoma clone N1E-115, which possesses receptors for neurotensin mediating the formation of intracellular cyclic GMP and the stimulation of inositol phospholipid hydrolysis, exhibited only partial desensitization to neurotensin. This result led to the observation that neurotensin was very rapidly degraded by intact N1E-115 cells. In experiments measuring the time course of [3H]neurotensin degradation, a minimum of six major tritiated products were found, with the breakdown peptides formed and the degree of proteolysis of [3H]neurotensin being dependent upon the length of incubation and the concentration of cells. Clone N1E-115 degraded [3H]neurotensin in an apparently sequential fashion; the primary initial cleavage of intact neurotensin was at the peptide bond between residues Arg8 and Arg9. Initial degradation peptides from the active carboxyl-terminal portion of neurotensin were more rapidly degraded, after formation, than were the peptides from the inactive amino-terminal half of neurotensin. The final two degradation products found were tyrosine, from the carboxyl-terminal portion of neurotensin, and an as yet unidentified peptide from the amino-terminal half of neurotensin. [3H]Neurotensin(8-13) was more rapidly hydrolyzed under identical conditions than was [3H]neurotensin itself. A combination of the protease inhibitors 1,10-phenanthroline and Z-Pro-Prolinal was able to inhibit almost completely the degradation of neurotensin by clone N1E-115.
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PMID:Rapid degradation of neurotensin by intact murine neuroblastoma cells (clone N1E-115). 368 1


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