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

Accumulation of inositol phosphates in NG108-15 neuroblastoma x glioma hybrid cells, pre-labeled for 24h to equilibrium, was stimulated by bradykinin, guanosine 5'-O-(3-thiotriphosphate) and the diacylglycerol kinase inhibitor R59022. Only the stimulation by bradykinin was inhibited by the bradykinin receptor antagonist [D-Arg0, Hyp3, Phe7, Thi5,8] bradykinin. Neither bradykinin nor R059022 increased the labeling of the inositol phospholipids. The sulfhydryl-alkylating reagent N-ethylmaleimide at 100 microM essentially abolished the stimulation caused by all three agents, possibly by preventing the binding of GTP to a guanine nucleotide-binding regulatory protein of as yet unknown size.
 ...
PMID:Effects of bradykinin, GTP gamma S, R59022 and N-ethylmaleimide on inositol phosphate production in NG108-15 cells. 268 44

The anti-helminthic drug suramin inhibited the basal high-affinity GTPase activity of both C6 BU1 glioma and NG 108-15 neuroblastoma x glioma hybrid-cell membranes with an IC50 (concentration causing half-maximal inhibition) value close to 30 micrograms/ml. This effect was shown to occur via a non-competitive mechanism in which the binding affinity of the G-proteins for GTP was not altered, but the maximal velocity of the subsequent hydrolysis was reduced. In NG 108-15 membranes, both opioid peptides and foetal-calf serum stimulated high-affinity GTPase activity in a pertussis-toxin-sensitive manner. These effects have previously been shown to be mediated by different G-proteins [McKenzie, Kelly, Unson, Spiegel & Milligan (1988) Biochem. J. 249, 653-659]. Suramin completely prevented the opioid-peptide-stimulated increase in GTP hydrolysis, but did not prevent the opioid peptide from binding to its receptor. Suramin, however, did not block the foetal-calf-serum-stimulated GTPase response. This selective action of suramin provides further evidence for distinct roles for two separate pertussis-toxin-sensitive G-proteins in signal transduction in NG 108-15 membranes and provides the first evidence for a selective effect of a drug on the functions of different G-proteins.
 ...
PMID:Differential effects of suramin on the coupling of receptors to individual species of pertussis-toxin-sensitive guanine-nucleotide-binding proteins. 283 58

The net content of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] was measured in bradykinin (BK)-stimulated NIH3T3 fibroblasts and neuroblastoma-glioma hybrid cells (NG108-15). BK-mediated production of Ins(1,4,5)P3 was not affected by replacing the medium with Ca2+-free medium, but addition of EGTA (1mM) to Ca2+-free medium markedly prevented production of Ins(1,4,5)P3. Although pertussis toxin (PT) treatment caused ADP-ribosylation in both NIH3T3 cells and NG108-15 cells, the BK-induced Ins(1,4,5)P3 formation was considerably reduced in the former cells but not in the latter cells, suggesting that PT-sensitive and PT-insensitive GTP-binding proteins are involved in phosphoinositide phospholipase C (PI-PLC) activation in fibroblasts and neuroblastoma cells, respectively. In NG108-15 cells down-regulated in protein kinase C (PKC) by long-term exposure to phorbol 12-myristate 13-acetate (PMA), BK-stimulated Ins(1,4,5)P3 accumulation was significantly enhanced compared to control cells.
 ...
PMID:Bradykinin-induced generation of inositol 1,4,5-trisphosphate in fibroblasts and neuroblastoma cells: effect of pertussis toxin, extracellular calcium, and down-regulation of protein kinase C. 284 40

Activation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells attenuates cyclic AMP accumulation. This effect results from an activation of phosphodiesterase with no direct inhibition of adenylate cyclase activity. In spite of this lack of coupling of muscarinic receptors to adenylate cyclase, guanine nucleotides reduce the apparent binding affinity of the agonist carbachol in a washed membrane preparation of 1321N1 cells. The order of potency for this effect is guanosine 5'-O-(3-thiotriphosphate) greater than 5'-guanylyl-imidodiphosphate = GTP = GDP; ATP has no effect. The occurrence of a Mr = 41,000 protein labeled in the presence of [32P]NAD and pertussis toxin as well as the occurrence of guanine nucleotide-mediated inhibition of forskolin-stimulated adenylate cyclase activity indicate that the functional inhibitory guanine nucleotide regulatory component of adenylate cyclase (Ni) is present in 1321N1 cells. Pertussis toxin pretreatment of NG108-15 neuroblastoma X glioma cells, which express muscarinic receptors that link through Ni to inhibit adenylate cyclase, blocked the GTP-sensitive, high affinity binding of carbachol. In contrast, pretreatment of 1321N1 cells with a concentration of pertussis toxin that blocked [32P]ADP ribosylation of the Mr = 41,000 substrate and GTP-mediated inhibition of forskolin-stimulated adenylate cyclase activity had no effect on GTP-sensitive high affinity binding of carbachol. These results suggest that muscarinic cholinergic receptors of 1321N1 cells couple to a guanine nucleotide regulatory protein that is distinct from Ni.
 ...
PMID:Guanine nucleotide-sensitive, high affinity binding of carbachol to muscarinic cholinergic receptors of 1321N1 astrocytoma cells is insensitive to pertussis toxin. 298

The existence of multiple affinity states for the opiate receptor in neuroblastoma x glioma NG108-15 hybrid cells has been demonstrated by competition binding studies with tritiated diprenorphine and [D-Ala2, D-Leu5]enkephalin (DADLE). In the presence of 10 mM Mg2+, all receptors exist in a high affinity state with Kd = 1.88 +/- 0.16 nM. Addition of 10 microM guanyl-5'-yl imidodiphosphate (Gpp(NH)p) decreased the affinity of DADLE to Kd = 8.08 +/- 0.93 nM. However, in the presence of 100 mM Na+, which is required for opiate inhibition of adenylate cyclase activity, analysis of competition binding data revealed three sites: the first, consisting of 17.5% of total receptor population has a Kd = 0.38 +/- 0.18 nM; the second, 50.6% of the population, has a Kd = 6.8 +/- 2.2 nM; and the third, 31.9% of the population, has a Kd of 410 +/- 110 nM. Thus, in the presence of sodium, a high affinity complex between receptor (R), GTP binding component (Ni), and ligand (L) was formed which was different from that formed in the absence of sodium. These multiple affinity states of receptor in the hybrid cells are agonist-specific, and the percentage of total opiate receptor in high affinity state is relatively constant in various concentrations of Na+. Multiple affinity states of opiate receptor can be demonstrated further by Scatchard analysis of saturation binding studies with [3H]DADLE. In the presence of Mg2+, or Gpp(NH)p, analysis of [3H]DADLE binding demonstrates that opiate receptor can exist in a single affinity state, with apparent Kd values of [3H]DADLE in 10 mM Mg2+ = 1.75 +/- 0.28 nM and in 10 microM Gpp(NH)p = 0.85 +/- 0.12 nM. There is a reduction of Bmax value from 0.19 +/- 0.02 nM in the presence of Mg2+ to 0.14 +/- 0.03 nM in the presence of Gpp(NH)p. In the presence of 100 mM Na+, Scatchard analysis of saturation binding of [3H]DADLE reveals nonlinear plots; two-site analysis of the curves yields Kd = 0.43 +/- 0.09 and 7.9 +/- 3.2 nM. These Kd values are analogous to that obtained with competition binding studies. Again, this conversion of single site binding Scatchard plots to multiple sites binding plots in the presence of Na+ is restricted to 3H-agonist binding only.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Multiple affinity states of opiate receptor in neuroblastoma x glioma NG108-15 hybrid cells. Opiate agonist association rate is a function of receptor occupancy. 298 65

The inhibition of adenylate cyclase activity by cannabimimetic compounds in a membrane fraction from cultured neuroblastoma cells has been examined. The inhibition was shown to be concentration-dependent over a nanomolar range for both delta 9-tetrahydrocannabinol and its synthetic analog, desacetyllevonantradol. Inhibition was rapid and reversible. The cannabimimetic compounds caused a decrease in Vmax of the enzyme, with no alteration in the Km for substrate. The effects of these compounds were related to the ability of the enzyme to be regulated by divalent cations and guanine nucleotides. The inhibition was greatest at micromolar Mg2+ or Mn2+ concentrations and was abolished at less than 1 mM MnCl2. In the hormone-stimulated state, the enzyme appeared to be regulated by one Mg2+ site. The addition of cannabimimetic or muscarinic cholinergic agents transformed the enzyme into one in which more complex regulation by divalent cations was observed. Half-maximal inhibition of adenylate cyclase was observed at 800 nM GTP for both cannabimimetic and muscarinic cholinergic agents. The substitution for GTP of a nonhydrolyzable analog resulted in activation of the enzyme and failure to respond to either class of inhibitory agents. If the Mg2+ concentration was reduced and exposure to the GTP analog was of short duration, inhibition by both cannabimimetic and muscarinic agents could be observed in the presence of forskolin. This study points to the similarities between the enzyme inhibition by cannabimimetic compounds and by muscarinic cholinergic compounds. It is inferred that the cannabimimetic compounds must act via regulatory mechanisms similar to those operating for receptor-mediated inhibition of adenylate cyclase.
 ...
PMID:Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. 298 38

In membranes of neuroblastoma x glioma hybrid (NG108-15) cells, bradykinin (EC50 approximately equal to 5 nM) stimulates GTP hydrolysis by a high-affinity GTPase (Km approximately equal to 0.2 microM). The octapeptide, des-Arg9-bradykinin, was inactive. Stimulation of GTP hydrolysis by bradykinin and an opioid agonist was partially additive. Treatment of NG108-15 cells with pertussis toxin, which inactivates Ni, eliminated GTPase stimulation by the opioid agonist but not by bradykinin. The data suggest that bradykinin activates in NG108-15 membranes a guanine nucleotide-binding protein which is not sensitive to pertussis toxin and which may be involved in bradykinin-induced stimulation of phosphoinositide metabolism in these cells.
 ...
PMID:Bradykinin stimulates GTP hydrolysis in NG108-15 membranes by a high-affinity, pertussis toxin-insensitive GTPase. 300 34

The tridecapeptide, neurotensin, inhibited prostaglandin E1-stimulated cyclic AMP production in intact plated neuroblastoma N1E115 cells. The peptide effect was concentration dependent (EC50 = 2 nM) and maximal inhibition reached 55% with 100 nM neurotensin. Acetyl neurotensin (8-13) was as active as neurotensin whereas neurotensins (1-8), (1-12), and (10-13) were barely active in inhibiting cyclic AMP production, thus showing the requirement of the carboxy terminal hexapeptide sequence of neurotensin for biological activity. The inhibitory effect of neurotensin on cyclic AMP production was largely prevented by pretreatment of N1E115 cells with islet-activating protein (pertussis toxin). In contrast, pertussis toxin did not inhibit neurotensin-stimulated cyclic GMP production in neuroblastoma cells. In cell membranes, the toxin promoted the selective ADP-ribosylation of a single protein having the same molecular weight (41,000) as the alpha-subunit of Ni, the inhibitory regulatory protein of adenylate cyclase. In membranes prepared from N1E115 cells, monoiodo[125I-Tyr3]neurotensin bound to a single population of receptors characterized, at 25 degrees and in the absence of monovalent cations and guanyl nucleotides, by a dissociation constant (Kd) of 56 pM and a maximal binding capacity (Bm) of 30 fmol/mg of protein. Na+ (10-100 mM) and GTP (0.1-100 microM) inhibited neurotensin binding in a concentration-dependent manner. At 100 mM Na+ and 100 microM GTP, receptor affinity was decreased by 5- and 2-fold, respectively. Li+ and K+ were less effective than Na+, and the effect of GTP was shared by GDP and guanyl-5'-yl-imidodiphosphate, but not by GMP, ATP, ADP, or adenyl-5'-yl-imidodiphosphate. It is concluded that in N1E115 cells, neurotensin attenuates cyclic AMP production by exerting an inhibitory effect on adenylate cyclase through an interaction of the peptide receptors with the regulatory GTP-binding protein Ni.
 ...
PMID:Neurotensin-mediated inhibition of cyclic AMP formation in neuroblastoma N1E115 cells: involvement of the inhibitory GTP-binding component of adenylate cyclase. 301 77

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.
 ...
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.
 ...
PMID:Functional properties and molecular structure of central and peripheral neurotensin receptors. 304 Sep 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>