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)

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors. Two different aspects of the blocking effect were detected, a resting block and a recovery from block during prolonged depolarizing pulses. Recovery from block was more complete, and its time course was more rapid, with depolarization to more positive potentials. The dose dependence of the type 2 channel block at rest indicated a one-to-one binding stoichiometry, with an apparent dissociation constant of 8.8 nM. Somatostatin exerted a similar selective blocking action on the type 2 Ca2+ channel. The time- and voltage-dependent block of type 2 Ca2+ channels may provide a mechanism underlying the enkephalinergic presynaptic inhibition of transmitter release and the somatostatin block of pituitary growth hormone release.
 ...
PMID:Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells. 243 4

The carboxy terminal part of the proenkephalin A sequence is the 31 amino acid peptide B, which has as its final seven amino acids the sequence of the opioid peptide Met-enkephalyl-Arg6-Phe7. Using a radioimmunoassay which recognises both these peptides we have investigated the relative amounts of peptide B and Met-enkephalyl-Arg6-Phe7 in a human neuroblastoma cell line. We show that these cells contain peptide B-like immunoreactivity but not its heptapeptide fragment. This may be due to lack of proteolytic activity cleaving Met-enkephalyl-Arg6-Phe7 from its precursor, peptide B. On treatment with dibutyryl cyclic AMP the level of immunoreactivity approximately doubles, due to increased amounts of peptide B-like immunoreactivity. Treatment with reserpine, which increases conversion of peptide B to the heptapeptide in bovine chromaffin cells in culture does not stimulate the accumulation of Met-enkephalyl-Arg6-Phe7 in the human neuroblastoma cells. The results are discussed with respect to peptide processing.
 ...
PMID:Met-enkephalyl-Arg6-Phe7 immunoreactivity in a human neuroblastoma cell line: effect of dibutyryl 3':5'-cyclic AMP and reserpine. 243 54

Substance P at micromolar concentrations enhances the uptake of [14C]guanidinium in neuroblastoma X glioma hybrid cells, an effect which most likely indicates activation of Na+ permeability. The substance P receptor was characterized pharmacologically. Analogues of substance P with D-amino acids e.g. spantide, and substance P-methyl ester were similarly active. Substance P (free acid), fragments of the substance P precursor, and substance P-(1-9) displayed no activity. This indicates the importance of the hydrophobic C-terminal for stimulation of the hybrid cells. The potency was reduced with decreasing length the of C-terminal fragments. However, the substance P antagonists [D-Pro4,D-Trp7,9,Nle11]substance P-(4-11) and [D-Pro4,D-Trp7,9,10]substance P-(4-11) showed substantially greater activity than substance P-(4-11). Substance P-(6-11) (i.e. H-Arg-DTrp-MePhe-DTrp-Leu-Met-NH2) behaved as a mixed agonist-antagonist. At concentrations higher than 10 microM, it inhibited the stimulation exerted by substance P. No other peptides of the tachykinin family (neurokinins A and B, physalaemin, eledoisin, kassinin) nor the synthetic analogues with specificity for certain receptor subtypes ([pGlu6,Pro9]substance P-(6-11), DiMe-C7, i.e. [pGlu5,MePhe8,Sar9]substance P-(5-11) and senktide, i.e. N-succinyl-[Asp6,MePhe8]substance P-(6-11) had any effect on guanidinium uptake in the hybrid cells. Hence, the substance P site with low affinity on the hybrid cells does not fit into the usual classification of tachykinin receptors but resembles the site that modulates nicotinic acetylcholine receptors on chromaffin cells.
 ...
PMID:Characterization of a substance P receptor activating a cation permeability in neuronal cell lines. 245 Jul 63

Effect of chloramine-T, the specific reagent on methionine residues, on gating of sodium channels was studied in neuroblastoma cell membrane. After the chloramine treatment the inactivation became slower, incomplete and the steepness of its voltage dependence considerably decreased; the inactivation curve was shifted towards depolarization. Time course of activation did not change. The activation curve shifted towards negative potentials, its slope being insignificantly decreased. Effective charge of activation as determined from the limiting logarithmic slope of the activation decreased by a factor of 1.17. Possible explanations of the phenomena observed are discussed.
 ...
PMID:[Action of chloramine-T on the processes of sodium channel activation and inactivation in neuroblastoma cells]. 245 54

Monoclonal antibodies (MAB) were developed which recognize a peptide, His-Glu-Ala-Pro-Ile (HEAPI), encoded by the RNA complementary to the mRNA specifying [Met]-enkephalin. One such MAB (designated 6193) exhibited a high degree of reactivity to the peptide sequence. Other characteristics of 6193 MAB include: the ability to block opioid ligand binding in a radioreceptor assay; agonist activity similar to opioid peptides in suppressing cAMP production; and the recognition of a 58 kDa protein on the surface of the neuroblastoma x glioma cell line, NG108-15. These results are consistent with a reactivity of 6193 MAB with the delta-class opioid receptor.
 ...
PMID:Monoclonal antibody against a peptide specified by [Met]-enkephalin complementary RNA recognizes the delta-class opioid receptor. 246 48

The endogenous opioids and their receptors are known to play a major role in neoplasia. In the present study, naltrexone (NTX), a potent opioid antagonist, was utilized to explore the interactions of opioids and opioid receptors in mice with transplanted neuroblastoma (S20Y). Tumors from mice subjected to either intermittent (4-6h/day; 0.1 mg/kg NTX) or complete (24 h/day; 10 mg/kg NTX) opioid receptor blockade exhibited an up-regulation of DADLE and Met-enkephalin binding sites, as well as tissue levels of beta-endorphin and Met-enkephalin. Binding affinity to [D-Ala2,D-Leu5]enkephalin (DADLE) or ethylketocyclazocine (EKC), the levels of plasma beta-endorphin, and the anatomical location and quantity of Met- and Leu-enkephalin and cytoskeletal components (i.e. tubulin, actin, brain spectrin (240/235) were similar in NTX and control tumor-bearing animals. Tissue viability of the 0.1 NTX group was increased compared to controls. Both mitotic and labeling indexes were increased during the period of opioid receptor blockade, but decreased in the period subsequent to receptor blockade. NTX treatment produced a 2-fold increased in sensitivity to opioids. Met-enkephalin (10 mg/kg) produced a depression in both mitotic and labeling indexes in tumor-bearing mice that could be reversed by naloxone (10 mg/kg) administration. Thus, the endogenous opioids are trophic agents that inhibit growth by suppressing cell proliferation. The duration of receptor blockade by opioid antagonists modulates these actions, affecting both tumor incidence and survival time. Complete opioid receptor block prevents the interaction of increased levels of putative growth-related peptides with a greater number of opioid receptors, thereby increasing cell proliferation and accelerating tumor growth. With intermittent blockade, an enhanced opioid-receptor interaction occurs during the interval when the opioid antagonist is no longer present, producing an exaggerated inhibitory action on cell proliferation and the repression of tumorigenic events.
 ...
PMID:Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. 254 Aug 73

A panel of seven murine monoclonal antibodies reactive with human hepatocellular carcinoma (HCC) cell line, SK- HEP-1, resulted in the definition of four distinct antigen systems, designated HB4, HB5, HB1 and HJ2. HB4 antigen was found to be expressed specifically on HCC cell lines and fresh HCC specimens but not on normal liver. Immunoprecipitation tests suggest that the HB4 epitope may be a heat-stable carbohydrate determinant on a high molecular mass molecule. HB5 antigen was found to have less-restricted expression on a panel of normal adult tissues and on melanoma, astrocytoma, sarcoma, neuroblastoma and epithelial cancer cell lines. In fetal and adult liver, HB5 antigen localized to bile canaliculi and ducts. Under reducing conditions, three mAbs detected a Mr 140,000 glycoprotein using lysates of [125-I], [3-H]-glucosamine and [35-S]-methionine labeled SK-HEP-1 cells. Under non-reducing conditions an additional component of greater than Mr 200,000 was also detected. HB1 antigen was found on almost all monolayer cell lines and not on most cultured suspension cells. This antigen was also detected on cultured HCC cells inoculated into nu/nu mice. Immunoprecipitation experiments revealed that the HB1 antigen is a bimolecular complex with an Mr 170,000 alpha chain and Mr 130,000 beta chain under non-reducing conditions, and three subunits of Mr 140,000, Mr 30,000 and Mr 130,000 under reducing conditions. Two antibodies reacted with epitopes on the alpha chain. HJ2 antigenic determinant is a heat-stable component which could not be immunoprecipitated. This most widely expressed antigen was found in secreted form in many of the cells and tissues examined. These antibodies introduce new antigens which may serve as useful markers for the diagnosis, classification and investigation of HCC and other liver diseases.
 ...
PMID:Serological analysis and biochemical characterization of monoclonal antibodies defining antigens of human hepatocellular carcinoma. 255 3

P-glycoprotein is a plasma membrane protein believed to mediate resistance to natural product drugs such as vincristine, Adriamycin, and actinomycin D. To facilitate the study of human P-glycoprotein, monoclonal antibodies (designated HYB-612, HYB-241, and HYB-195) were raised against vincristine-resistant human neuroblastoma (SH-SY5Y/VCR) cells. The antibodies recognize a Mr 180,000 plasma membrane phosphoglycoprotein produced in increased amounts in SH-SY5Y/VCR as well as in vincristine-resistant human neuroepithelioma (MC-IXC/VCR), vinblastine-resistant human leukemia (CEM/VLB100), and actinomycin D- or vincristine-resistant Chinese hamster (DC-3F/AD X and DC-3F/VCRd-5L) cells, as compared to control cells. Radioimmunoprecipitation of proteins in cells metabolically labeled with [35S]methionine, 32Pi, or [3H]glucosamine and Western transfer procedures were used for these studies. Characterization of the HYB-612 or HYB-241 antigen by destructive degradation produced a pattern of results typical of a conformation-dependent protein epitope. HYB-612 recognizes complexes of the Mr 180,000 antigen with an iodinated photoaffinity analogue of vinblastine or with tritiated azidopine. Furthermore, pretreatment of MC-IXC and MC-IXC/VCR cells with HYB-612 or HYB-241 before measurement of tritium-labeled actinomycin D or vincristine uptake increases the amount of drug accumulation in resistant, but not in sensitive, cells. Of importance is the fact that the Mr 180,000 protein is expressed in cells which also contain a Mr 170,000 P-glycoprotein. The relative amounts of the Mr 180,000 and 170,000 species vary from one drug-resistant cell line to another. Evidence that the Mr 180,000 protein is a P-glycoprotein and that there is a conserved complex pattern of resistance-related surface proteins in multidrug-resistant cells is presented in this report.
 ...
PMID:Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells. 256 79

Protein carboxylmethyltransferase has been proposed to play a role in the regulation of neuroblastoma differentiation (Kloog et al., 1983). When we investigated this hypothesis further, different results for methyl ester formation were obtained when measured in acid-precipitated proteins and in proteins separated by acidic polyacrylamide gel electrophoresis, following the incubation of intact neuroblastoma cells with [3H]methionine. These unexpected findings led to the development of a modified assay using S-[3H]-adenosylmethionine as the radiolabeled precursor for quantitating carboxyl methylation in intact cells. Data obtained from either acid-precipitated proteins or those separated on an electrophoresis gel following S-[3H]adenosylmethionine incubation directly correlated with data obtained from proteins separated by electrophoresis following [3H]methionine incubation. Using each of the three methods, an approximately twofold increase in the carboxyl methylation of cellular proteins was detected in neuroblastoma cells differentiated by reducing the serum concentration from 10 to 0.5%, but not in those cells differentiated with either 5 mM hexamethylene bisacetamide or 2% dimethyl sulfoxide. The finding that all detectable methyl acceptor proteins are increasingly methylated following 0.5% serum treatment and that this modification is substoichiometric suggests that protein carboxyl methylation is not an essential component of the differentiation process in neuroblastoma cells.
 ...
PMID:Protein carboxylmethyltransferase activity in intact, differentiated neuroblastoma cells: quantitation by S-[3H]adenosylmethionine prelabeling. 267 Dec 63

Clinical studies have suggested that the early stages of bilirubin encephalopathy are reversible. These phenomena are investigated at the cellular level using the neuroblastoma cell line N-115 as a model system. To determine whether the cell line N-115 can recover from bilirubin toxicity, and whether the cellular function remains intact after a short period of bilirubin exposure during which time no toxic effects are manifest, the cells are exposed to bilirubin at varying concentrations and varying bilirubin:albumin ratios for 1 and 2 h. The bilirubin is then washed out, and the cells are reincubated in fresh media with appropriate amounts of albumin. Mitochondrial function, [3H]thymidine uptake and L-[35S]methionine uptake are assessed at 2, 8, and 24 h of reincubation after the bilirubin washout. After the short-term exposure, the cells begin to demonstrate evidence of toxicity in all parameters measured 8-24 h after the bilirubin washout. After the 2-h exposure to bilirubin, the cells demonstrate significant toxicity within 2 h of the bilirubin washout. The degree of toxicity seems to depend on the bilirubin:albumin ratio and bilirubin concentration. In general, after bilirubin exposure of 1 h or longer, the N-115 cells develop evidence of toxicity which is progressive and irreversible.
 ...
PMID:Bilirubin toxicity in a neuroblastoma cell line N-115: II. Delayed effects and recovery. 272 10


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