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)

A method for assessing the binding of 3H-labeled prostaglandin E1 ([3H]PGE1) to cell membranes has been developed and used to study the interaction of [3H]PGE1 with membranes from cultured mammalian cells. Receptor sites were identified by correlation of the potency of a series of compounds to compete for [3H]PGE1 binding sites and to stimulate adenylate cyclase activity, by correlation of rates of binding and change in enzyme activity, and by the correspondence of [3H]PGE1-binding activity with the presence or absence of PGE1-sensitive adenylate cyclase in several clones. In clone B82, a murine L-cell, [3H]PGE1 binds with an activation energy of 14 kcal/mol to a class of sites with an affinity of 0.5 X 10(8) M-1 and a capacity of 150 fmol/mg of protein. Concentration dependence of adenylate cyclase activation by PGE1 (KD =30 nM) and kinetic analysis of [3H]PGE1 binding (k1 = 4 X 10(6) liters/mol/min, k-1 0.15/min) verify this affinity. Concentration dependence and specificity of binding and activation of adenylate cyclases in neuroblastoma clone N4TG1 and N18TG2 substantiate the method. In several clones that lack PGE1-responsive adenylate cyclase, no specific [3H]PGE1 binding is detectable.
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PMID:Binding of (3H)prostaglandin E1 to putative receptors linked to adenylate cyclase of cultured cell clones. 0 51

(-)-Norepinephrine and other catecholamines inhibit basal and prostaglandin E1-stimulated adenylate cyclase activities by 35 to 60% in homogenates of NG108-15 neuroblastoma x gloma hybrid cells and markedly reduce adenosine 3'35:'-monophosphate levels of intact cells, but do not affect guanosine 3':5'-monophosphate levels. The specificity of the NG108-15 receptor for ligands is that of an alpha receptor, possibly a presynaptic alpha 2 receptor. The inhibition of adenylate cyclase by norepinephrine is reversed by alpha receptor antagonists such as dihydroergotamine or phentolamine, but not by the beta receptor antagonist propranolol. The effect of norepinephrine on adenylate cyclase activity initially is dependent on GTP; half-maximal inhibition of enzyme activity by norepinephrine is obtained with 0.2 micron GTP. The inhibition of adenylate cyclase activity by norepinephrine is reduced by 10 mM NaF and is abolished by 0.05 mM guanyl-5'-yl imidodiphosphate. Inhibitions of NG108-15 adenylate cyclase mediated by alpha receptors, opiate receptors, and muscarinic acetylcholine receptors are not additive; this suggests that the three species of receptors can be functionally coupled to the same adenylate cyclase molecules or molecules regulating the enzyme.
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PMID:Regulation of adenylate cyclase of neuroblastoma x glioma hybrid cells by alpha-adrenergic receptors. I. Inhibition of adenylate cyclase mediated by alpha receptors. 3 89

The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of ""differentiated" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE1 and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3:5-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP protentiated the PGE1 effect in differentiated concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of Km and Vmax of neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE1 stimulated enzyme activity to GTP increase in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells.
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PMID:Effect of neurotransmitters, Guanosine triphosphate, and divalent ions on the regulation of adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate-induced "differentiated" neuroblastoma cells. 16 67

The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter.
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PMID:Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors? 19 42

C6 glioma cells and B104 neuroblastoma cells both possess adenylate cyclase activity, but only C6 cells have beta-adrenergic receptors. However, when cocultured with B104 cells, C6 cells show a marked decrease in their ability to accumulate adenosine 3', 5'-monophosphate upon stimulation with beta receptor agonists. Since both beta receptors and cholera toxin-stimulated adenylate cyclase activities are present in C6/B104 cocultures, we conclude that the beta receptor/adenylate cyclase transduction mechanism in cocultured C6 cells is uncoupled.
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PMID:Cellular interactions uncouple beta-adrenergic receptors from adenylate cyclase. 21 32

Neuroblastoma x glioma in NG108-15 cells possess opiate, alpha-adrenergic, and muscarinic acetylcholine receptors, which mediate an inhibition of adenylate cyclase. Growth of cells for 12--48 hours in the presence of a receptor--activator gradually results in a compensatory increase in adenylate cyclase activity. Withdrawal of the receptor ligand then results in relatively long-lived increases in adenylate cyclase activity and intracellular cAMP levels. Thus cells grown in the presence of morphine, norepinephrine, or acetylcholine seem to become dependent on the compound to maintain normal cAMP levels.
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PMID:Studies on synapse formation and opiate dependence. 21 60

Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma--brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of NIE-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and NIE-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that (i) NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, (ii) activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and (iii) serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.
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PMID:Adenylate cyclase and acetylcholine release regulated by separate serotonin receptors of somatic cell hybrids. 22 Jun 7

Inhibition of the adenylate cyclase activity in homogenates of mouse neuroblastoma-glioma hybrid cells (NG108-15) by the opioid peptide [D-Ala2,Met5]enkephalin amide (AMEA) requires the presence of Na+ and GTP. In this process, the selectivity for monovalent cations is Na+ greater than or equal Li+ greater than K+ greater than choline+; ITP will replace GTP but ATP, UTP, or CTP will not. The apparent Km for Na+ is 20 mM and for GTP it is 1 microM. Under saturating Na+ and GTP conditions, the apparent Ki for AMEA-directed inhibition is 20 nM for basal and 100 nM for prostaglandin E1-activated adenylate cyclase activity. For both cyclase activities, maximal inhibition is only partial (i.e., approximately 55% of control in each case). In intact viable NG108-15 cells, the decrease in basal and prostaglandin E1-stimulated intracellular cyclic AMP concentrations by AMEA is also dependent upon extracellular Na+. The enkephalin-directed reductions in cyclic AMP concentrations are at least 75%. The specificity of the monovalent cation requirement for enkephalin action on intact cells is the same as for enkephalin regulation of homogenate adenylate cyclase activity. Based on these data, a model is presented in which the transfer of information from opiate receptors to adenylate cyclase requires active separate membrane components, which correspond to the sites of action of Na+ and GTP in this process.
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PMID:Coupling of opiate receptors to adenylate cyclase: requirement for Na+ and GTP. 23 Apr 86

The distribution of prostaglandin D synthetase activity was determined in various tissues of rat by using the supernatant fraction (10,000 x g, 20 min) of the homogenates. The highest activity was found in brain, spinal cord, and alimentary tract. The activity was uniquitously distributed in all parts of brain, and the highest specific activity was found in hypothalamus and thalamus. Homogenates of two neuroblastoma cell lines were found to produce prostaglandin D2, whereas a glioma cell line was almost inactive. Prostaglandin D2 is a potent and specific activator of the adenylate cyclase system of cultured neuroblastoma cells, suggesting the possibility that it may act as a neuromodulator in the central nervous system.
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PMID:Prostaglandin D2, a neuromodulator. 23 May 3

Neuroblastoma cells were synchronized by a combined isoleucine plus glutamine starvation. Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was measured under basal conditions and in the presence of dopamine, adenosine and prostaglandin (PG) E1. A clear dissociation occurred between the respective evolution patterns of basal and agonist-stimulated adenylate cyclase activities. The magnitudes of the enzyme response to PGE1, adenosine, and dopamine also exhibited different evolution patterns during the cell cycle. Evolution of adenylate cyclase responsiveness to PGE1 during the cell cycle exhibited striking similarities with the intracellular 3':5'-cyclic AMP changes observed elsewhere. Use of theophylline and fluphenazine as specific inhibitors of adenosine and dopamine, respectively, made it possible to demonstrate that adenosine, dopamine, and PGE1 stimulated adenylate cyclase through independent receptor sites. Furthermore, whatever the stage of the cell cycle, responses to these three agonists were not additive, indicating that the receptors of adenosine, dopamine, and PGE1 control the same adenylate cyclase moieties. The data suggest that adenylate cyclase cell content and enzyme responsiveness to specific agonists can be independently controlled.
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PMID:Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. 26 97


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