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

Intracellular cyclic GMP content responds to the stimulation of muscarinic receptor in a variety of tissues. Several aspects of the cellular mechanism involved in the synthesis of cyclic GMP were investigated. 1. In cultured bovine chromaffin cells, acetylcholine as well as muscarine stimulated the 32Pi incorporation into phosphatidic acid, induced Ca2+ mobilization across the cells, and, in parallel, elevated intracellular cyclic GMP content. Phosphatidic acid added to culture medium also stimulated the efflux and influx of Ca2+ and the synthesis of cyclic GMP in bovine chromaffin cells and in neuroblastoma cells in the same fashion as acetylcholine. 2. We have succeeded in a purification of an endogenous activator for guanylate cyclase from rat brain and identified it as L-arginine. L-Arginine, but not D-arginine, activated soluble guanylate cyclase 10- to 20-fold at a low concentration (1-2 X 10(-5) M). The activation of the enzyme by L-arginine seemed to require Ca2+. Calcium accumulated in cells in response to muscarinic stimulation would activate guanylate cyclase in collaboration with L-arginine. 3. Using a specific monoclonal antibody, we demonstrated the cellular and subcellular localizations of guanylate cyclase in rat brain. An intense reaction was observed in the brain regions which were rich in muscarinic receptor. Electron microscopic examination revealed that guanylate cyclase was concentrated in the postsynaptic perikaryon and dendrites of some type of neurons indicating its involvement in neural transmission.
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PMID:Cellular mechanism involved in the synthesis of cyclic GMP in nervous tissues. 613 49

Cells of the murine neuroblastoma clone N1E-115 possess muscarinic receptors that influence the intracellular level of cyclic nucleotides. The stimulation of [3H]cyclic GMP levels occurs only with intact cells and has an EC50 near the "low-affinity" agonist equilibrium dissociation constant (KL) determined by radioligand binding assays. The inhibition of prostaglandin E1-stimulated [3H]cyclic AMP formation has an EC50 close to the value for the "high-affinity" agonist equilibrium dissociation constant (KH). During sequential subculturing in medium supplemented with newborn bovine serum, the inhibition of [3H]cyclic AMP was maintained, but the [3H]cyclic GMP response declined dramatically, and after 7 subculturings it was essentially absent. The time course for [3H]cyclic GMP formation in a late subculture with an 88% loss of the response was identical with the time course in early subcultures. A normal [3H]cyclic GMP response to bradykinin and histamine was demonstrated to be present in cells that had lost the [3H]cyclic GMP response to carbachol. The EC50 and KD values for the two muscarinic responses and binding sites increased 3- to 4-fold after several subculturings. A 90% loss of low-affinity binding sites was closely correlated with a similar loss of the [3H]cyclic GMP response. High-affinity binding sites did not decline significantly in concentration until the 11th subculture, where the total number of muscarinic sites was only 6% of the earliest subculture. In all subcultures, however, the ability of the muscarinic receptor to decrease [3H]cyclic AMP levels was maintained. These data, which show that the subculturing of N1E-115 cells in medium supplemented with newborn calf serum results in a selective loss of one muscarinic function, strongly support the hypothesis that these cells contain two separate muscarinic receptor-effector systems. One receptor subtype or conformation has a low affinity for the agonist and mediates cyclic GMP formation. The other receptor subtype or conformation has a higher affinity for the agonist and mediates an inhibition of prostaglandin E1-stimulated cyclic AMP formation.
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PMID:Muscarinic responses and binding in a murine neuroblastoma clone (N1E-115). Selective loss with subculturing of the low-affinity agonist site mediating cyclic GMP formation. 614 90

A clone of murine neuroblastoma (N1E-115) was shown to have functional receptors for the nonapeptide bradykinin. These receptors mediated a large, rapid (about 1 min to peak) and calcium-dependent increase in cyclic GMP. The median effective concentration (EC50) averaged 1.4 nM. In addition, this event was inhibited by quinacrine, 5,8,11,14-eicosatetraynoic acid, and nordi-hydroguaiaretic acid, suggesting involvement of phospholipase A2 with subsequent formation of lipoxygenase metabolities of arachidonic acid. [3H]Bradykinin binding to intact cells, investigated under conditions nearly identical to those used in the cyclic GMP assay, yielded binding sites with KDS of 0.83 pM, 1.0 nM, and 4.9 nM with respective Bmax values of 12, 160, and 250 fmol/10(6) cells. Apparently, the cyclic GMP response was associated with the binding site in which the KD = 1.0 nM. Peptide analogs of bradykinin stimulated cyclic GMP with EC50S nearly identical to their respective KDS determined in binding assays with [3H]bradykinin, thus providing evidence for receptor specificity of this response. This finding of a biochemical response of bradykinin promises to make N1E-115 cells a convenient model system for study of neuronal bradykinin receptors.
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PMID:Bradykinin receptor-mediated cyclic GMP formation in a nerve cell population (murine neuroblastoma clone N1E-115). 614 70

Incubation of mouse neuroblastoma cells (clone N1E-115) with Mn2+ resulted in a rapid and transient increase in cyclic GMP formation. This effect appears to be due to an increase in calcium influx because it did not occur in the absence of extracellular calcium or in the presence of verapamil, a calcium transport inhibitor. In addition, Mn2+ inhibited muscarinic receptor-mediated cyclic GMP responses. The ability of Mn2+ to increase cyclic GMP levels was markedly diminished in cells desensitized to the effects of carbamoylcholine, suggesting that this densensitization involves inactivation of calcium entry.
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PMID:Involvement of calcium channels in short-term desensitization of muscarinic receptor-mediated cyclic GMP formation in mouse neuroblastoma cells. 625 69

D-Ala2-Met5-enkephalin, morphine, and noradrenaline inhibit the adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells in a dose-dependent manner even after the enzyme has been preactivated by cholera toxin. Half-maximal inhibition and extent of inhibition are the same with native or cholera toxin-activated enzyme. The inhibition caused by opioids or noradrenaline are antagonized by naloxone or phentolamine, respectively. The effect of D-Ala2-Met5-enkephalin on cholera toxin-activated enzyme is immediate in onset and rapidly reversed by the addition of naloxone. Guanyl-5'-yl-imidodiphosphate stimulates basal activity but inhibits the enzyme activated by cholera toxin or prostaglandin E1. Stimulation occurs at a concentration of 100 microM or above, inhibition even at 0.1 microM. The inhibitory effect of the non-hydrolysable GTP analog is antagonized by GTP. Guanyl-5'-yl-methylenediphosphonate, another nonhydrolysable GTP analog, inhibits basal as well as cholera toxin-stimulated or prostaglandin E1-stimulated adenylate cyclase. Other guanine derivatives such as GDP, GMP, cyclic GMP, guanyl-5'-yl-phosphoric acid amide and guanosine have no effect under the same conditions. The results may be taken as a piece of evidence for two separate guanyl nucleotide-binding sites accompanying the adenylate cyclase in the hybrid cells and mediating, respectively, stimulation and inhibition of the enzyme by hormones.
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PMID:Opioids, noradrenaline and GTP analogs inhibit cholera toxin activated adenylate cyclase in neuroblastoma x glioma hybrid cells. 625 56

Cyclic-GMP-dependent protein kinase purified from bovine lung was radioiodinated by the Bolton-Hunter procedure yielding a specific radioactivity of 2200 Ci/mmol of enzyme, Using a specific precipitating rabbit antiserum to the cyclic-GMP-dependent protein kinase, a sensitive radioimmunoassay was developed which can detect 200 pg (1.33 fmol) of cyclic GMP-dependent protein kinase. Immunoreactivity like that of cyclic-GMP-dependent protein kinase was detectable in extracts of all rat tissues tested, in extracts of cultured rat brain and heart cells, and in extracts of rat glioma (C6) and neuroblastoma x glioma hybrid cells. In extracts of several tissues and cell lines the presence of cyclic-GMP-dependent protein kinase was also demonstrated by a photoaffinity-labeling procedure using 8-azidoinosine 3',5'-[32P]monophosphate. The results suggest that cyclic-GMP-dependent protein kinase is ubiquitously distributed although its level varies significantly from tissue to tissue and cell type to type. The results also support the hypothesis that cyclic-GMP-dependent protein kinase is involved in mediating some of the intracellular effects of those hormones, neurotransmitters and drugs which regulate the intracellular level of cyclic GMP.
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PMID:Distribution of cyclic-GMP-dependent protein kinase in various rat tissues and cell lines determined by a sensitive and specific radioimmunoassay. 626 53

Phosphatidic acid added to the medium markedly elevated intracellular cyclic GMP content in cultured neuroblastoma N1E 115 cells. There was a significant elevation of cyclic GMP with 1 micrograms/ml and a maximum (70-fold) elevation with 100 micrograms/ml of phosphatidic acid. Other natural phospholipids did not increase, or increased only slightly, the cyclic GMP content in the cells. The elevation of cyclic GMP content by phosphatidic acid was absolutely dependent on extracellular calcium. Phosphatidic acid stimulated the influx of calcium into neuroblastoma cells 2- to 5-fold. The pattern of the calcium influx induced by phosphatidic acid was comparable to that of cyclic GMP elevation. The stimulation of calcium influx by phosphatidic acid was also observed in cultured heart cells, indicating that phosphatidic acid acts as a calcium ionophore or opens a specific calcium-gate in a variety of cell membranes. Treatment of neuroblastoma cells with phospholipase C increased 32Pi labeling of phosphatidic acid, stimulated the influx of calcium, and elevated the cyclic GMP content in the cells. Thus exogenous as well as endogenous phosphatidic acid stimulates the translocation of calcium across cell membranes and, as a consequence, induces the synthesis of cyclic GMP in the neuroblastoma cells.
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PMID:Stimulation of phosphatidic acid of calcium influx and cyclic GMP synthesis in neuroblastoma cells. 627 Jan 38

Growth inhibitory factor for mouse neuroblastoma cells was detected in the culture medium of fetal rat glioblasts, and was partially purified and characterized. The factor had an apparent molecular weight of 75,000 and an isoelectric point of 5.8, and showed no esterase activity. It possessed the activity to promote morphological differentiation including the formation of neural processes and the inhibition of cell division when tested on mouse neuroblastoma cell lines (Neuro 2a, NS-20Y, and NIE-115). The activity was susceptible to protease digestion and heat treatment. The serum over 25% cancelled the inhibitory activity of this factor. The factor failed to increase the intracellular contents of cAMP and cGMP. It showed no effect on either morphological differentiation or proliferation of glial cell lines, suggesting that under physiological conditions the factor acts specifically on neuronal cells.
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PMID:Inhibition of growth of mouse neuroblastoma cels by protein factor derived from rat glioblasts. 628 Aug 7

1 Twenty-two compounds classified as antidepressants, metabolites of antidepressants or putative antidepressants were assayed for their ability to antagonize the binding of (-)-[3H]-quinuclidinyl benzilate to muscarinic receptors in homogenates of human caudate nucleus. 2 Sixteen of these compounds were assayed for their ability to antagonize carbachol-stimulated cyclic guanosine 3',5'-monophosphate (cyclic GMP) synthesis by intact murine neuroblastoma cells (clone N1E-115). 3 Equilibrium dissociation constants (KDs) for these drugs and the muscarinic receptors of human brain spanned over 4 orders of magnitude, with the tertiary amine tricyclic antidepressant, amitriptyline (KD = 18 nM) being the most potent compound tested and trazodone (KD = 324 microM) the least potent. 4 There was a significant correlation between the data for human and murine receptors and for eight compounds (imipramine, desipramine, maprotiline, mianserin, 3-chloro-2-hydroxyimipramine, amoxapine, 2-hydroxyimipramine and iprindole). KD values measured by the two techniques were not significantly different.
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PMID:Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. 629 50

Several calcium antagonists were screened for their effect on muscarinic acetylcholine receptor-mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Mn2+, Ni2+, and verapamil rapidly antagonized the response noncompetitively, with the following order of potency: verapamil greater than Mn2+ greater than Ni2+. The effects of Mn2+ and Ni2+, but not those of verapamil, were largely reversed by increasing extracellular calcium concentration. Additional effects of these agents included displacement of [3H]quinuclidinyl benzilate binding by verapamil and elevation of cyclic GMP levels by Mn2+ and Ni2+ in the absence of agonists. These results are in support of the hypothesis that receptor-mediated cyclic GMP formation by these cells is dependent upon entry of calcium into the cell and demonstrate the complexity of the effects of calcium antagonists.
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PMID:Effect of some calcium antagonists on muscarinic receptor-mediated cyclic GMP formation. 629 67


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