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)

Secretin receptors in membranes from the neuroblastoma-glioma hybrid cell line NG108-15 were investigated by 125I-secretin binding and adenylate cyclase activation. On both parameters the corresponding relative potencies of parent peptides were, respectively: secretin greater than helodermin greater than peptide histidine isoleucinamide = vasoactive intestinal peptide. With secretin analogs and secretin fragments, the order of potency for binding was: secretin = [Val5]secretin greater than [Ala2]secretin = [Ala11]secretin greater than [Ala4, Val5] secretin greater than [Ala4]secretin greater than [D-Phe4] secretin greater than [D-Phe2]secretin = secretin (2-27) greater than secretin (3-27) greater than secretin (7-27). Also, on adenylate cyclase, [D-Phe4]secretin, [D-Phe2]secretin, secretin (2-27) and secretin (3-27) were partial agonists while secretin (7-27) was ineffective. The differentiating agent N6,2'-O-dibutyryladenosine 3',5'-monophosphate (1 mM) increased the density of secretin receptors and secretin-stimulated adenylate cyclase activity after a lag period of 4 h. After incubation for 24 h, receptor number and enzyme activity were increased 4- and 3-fold, respectively. These effects were inhibited totally by 1 microgram/ml cycloheximide and halved by 5 micrograms/ml actinomycin D. They were mimicked by 1 mM sodium butyrate but were not reproduced by either 8-bromoadenosine 3',5'-monophosphate or the phosphodiesterase inhibitor rac-4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone.
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PMID:Secretin receptors in the neuroglioma hybrid cell line NG108-15. Characterization and regulation of their expression. 217 30

Retinoic acid (RA) induces partial differentiation of neuroblastoma (NB) cells in vitro. In the human NB line, SH-SY5Y (a neuroblastic subclone of SK-N-SH), RA was previously shown to enhance the stimulatory (PGE1) and inhibitory (opioid) regulation of adenylyl cyclase. Since these cells are also sensitive to cAMP stimulation by vasoactive intestinal peptide (VIP), we have tested the effects of RA on VIP receptor expression and function. Pretreatment of SH-SY5Y cells with 10 microM RA over 6 days dramatically increased VIP receptor number from approximately 3,000 to approximately 70,000 sites per cell and enhanced threefold the cAMP accumulation after external VIP addition, while VIP immunoreactive content in the cells increased 2-3-fold. In the light of the recently proposed autocrine function of VIP in this cell lineage, the strong enhancement of the VIP system may contribute to the differentiation effects of RA.
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PMID:Retinoic acid enhances VIP receptor expression and responsiveness in human neuroblastoma cell, SH-SY5Y. 254 14

The human precursor gene for vasoactive intestinal peptide (VIP) and PHM-27, a peptide that has an NH2-terminal histidine and COOH-terminal methionine amide and is closely related in sequence and activity to VIP, was detected with synthetic oligodeoxynucleotide probes. These specific hybridization segments were constructed according to the neuroblastoma VIP cDNA sequence and contained up to 39 bases. The gene structure was partly deduced by hybridization to synthetic oligodeoxynucleotide probes and partly by direct chemical nucleotide sequencing. Four exons were discovered thus far; among them are two short exons separated by a 0.75-kilobase DNA stretch, one encoding PHM-27 and the second encoding VIP (exons 1 and 2). Each of these two exons encodes both the hormone amino acid residues as well as the post-translational processing signal sequences. The 3' splice sites of the two exons contain an identical stretch of nine nucleotides. At the cDNA level, the 3' splice sites contain the same stretch of six nucleotides, which are identically spliced. The occurrence of VIP and PHM-27 coding sequences on two separate exons of the human genome and the homology of their 3' splice site may allow alternative RNA processing as discussed below.
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PMID:Coding sequences for vasoactive intestinal peptide and PHM-27 peptide are located on two adjacent exons in the human genome. 298 32

Activation of protein kinase C by phorbol esters such as phorbol 12-myristate 13-acetate (PMA), modulates responsiveness of the cyclase system in many cell types. In the neuroblastoma-hybrid cell line NCB-20, PMA causes a reduction in receptor-mediated accumulation of cyclic AMP. The reduction in receptor responses by PMA occurs within 3 min and is still apparent at 40 min. This occurs in a concentration-dependent manner with an EC50 for PMA of approx. 30 nM. Accumulations of cyclic AMP that are elicited by prostaglandin E2, vasoactive intestinal peptide or 2-chloroadenosine are decreased in the presence of PMA. Accumulations of cyclic AMP that are elicited by forskolin in the absence of a receptor agonist are unaffected by the presence of PMA. Inhibition of cyclic AMP generation by dopamine is not diminished by PMA suggesting the receptor input through the inhibitory Ni-guanyl nucleotide binding protein is still functional after PMA treatment. The generalized inhibition of receptor-mediated responses by PMA could be due to a protein kinase C-mediated phosphorylation of the stimulatory Ns-guanyl nucleotide binding protein, but other mechanisms are possible.
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PMID:Inhibition of receptor-mediated stimulation of cyclic AMP accumulation in neuroblastoma-hybrid NCB-20 cells by a phorbol ester. 304 Jan 24

A 18-month-old boy with stage 4 neuroblastoma needed intensive care because of prerenal acute renal failure related to an intractable watery diarrhoea syndrome occurring 10 months after the diagnosis of the primary tumor. This diarrhoea was in relation with a late hyperproduction of vasoactive intestinal peptide by the relapsing neuroblastoma itself and stopped with intravenous somatostatin administration.
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PMID:[Metastatic neuroblastoma with secondary hypersecretion of vasoactive intestinal peptide]. 320 Jun 52

The expression of a transfected plasmid containing 5.2 kilobases (kb) of 5' regulatory DNA sequence of the human vasoactive intestinal peptide (VIP) gene attached to coding sequences of the reporter gene chloramphenicol acetyltransferase (CAT) was compared with endogenous VIP expression in subclones of the human neuroblastoma cell line SK-N-SH. These subclones vary widely in basal and inducible quantities of VIP and its precursor mRNA and can be interconverted under specified culture conditions. Endogenous VIP immunoreactivity, detectable in all subclones, was lowest in the neuronal subclone SH-SY-5Y, whereas 15- to 25-fold higher levels were observed in the epithelial-appearing SH-EP and intermediate SH-IN subclones. Treatment with 10 nM phorbol 12-myristate 13-acetate (PMA) stimulated VIP peptide levels approximately 5-fold in SH-SY-5Y cells but did not increase appreciably VIP levels in the other subclones. Treatment with 2.5 microM forskolin resulted in less than 50% stimulation of VIP expression in all subclones. Levels of mRNA encoding the VIP precursor generally paralleled these differences in VIP immunoreactivity. In cells transfected with the VIP/CAT fusion gene, CAT activity reflected closely these differences in basal VIP expression and the changes in response to PMA and forskolin. Deletion of 2.7 kb of the most upstream sequences resulted in an 80-90% reduction in basal CAT activity in SH-IN, but not SH-SY-5Y cells, and resulted in an 80% reduction in PMA stimulation in SH-SY-5Y cells. Deletion to within 74 nucleotides of the transcription start site resulted in CAT expression in SH-IN cells that was only 3% of that seen with the full 5.2-kb flanking sequences and further diminished the remaining PMA responsiveness in SH-SY-5Y cells. The data indicate that important cell-type-specific transcription regulatory sequences reside greater than 2.5 kb upstream from the VIP transcription start site.
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PMID:Lineage-specific regulation of the vasoactive intestinal peptide gene in neuroblastoma cells is conferred by 5.2 kilobases of 5'-flanking sequence. 320 Aug 39

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

Vipomas are tumours which secrete vasoactive intestinal peptide (VIP) and present with severe watery diarrhoea (the Verner and Morrison syndrome). The tumours are usually pancreatic in adults and originate in the sympathetic nervous system in children (neuroblastoma). The diagnosis is confirmed by the finding of raised plasma VIP. The treatment of choice is surgical excision of the tumour which leads to the regression of the watery diarrhoea.
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PMID:[Vipomas]. 609 17

A 1 1/2 year old child developed profuse watery diarrhoea, shown to be due to excessive plasma vasoactive intestinal peptide (VIP) levels, whilst on treatment for metastatic neuroblastoma. Because it was unresponsive to alternative treatment, an attempt was made to control the diarrhoea with a somatostatin infusion. The attempt failed despite the fact that serum VIP levels were substantially reduced. Possible reasons for failure are discussed and the importance of plasma VIP as a marker for maturation in neuroblastoma emphasised.
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PMID:Intractable diarrhoea in a patient with vasoactive intestinal peptide-secreting neuroblastoma. Attempted control by somatostatin. 611 74

Secretin, a gut-brain peptide, elicited cyclic AMP production in a clone of neuroblastoma cells derived from the C1300 mouse tumor. Adenylate cyclase (EC 4.6.1.1) in plasma membranes from these cells was stimulated by secretin greater than vasoactive intestinal peptide greater than peptide histidine isoleucine amide, but not by the related peptides glucagon, gastric inhibitory polypeptide, or human growth hormone releasing factor. Hill coefficients for stimulation approximated one and the response to submaximal peptide concentrations was additive, as expected for hormones competing for a single receptor associated with the enzyme. Binding of 125I-labeled secretin to the neuroblastoma plasma membranes was saturable, time-dependent, and reversible. The KD determined from kinetic and equilibrium binding studies approximated 1 nM. The binding site displayed marked ligand specificity that paralleled that for stimulation of adenylate cyclase. The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin. These findings demonstrate the functional association of the secretin receptor with adenylate cyclase in neuronally derived cells.
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PMID:Secretin receptors on neuroblastoma cell membranes: characterization of 125I-labeled secretin binding and association with adenylate cyclase. 632 61


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