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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine, 2-chloroadenosine and prostaglandin E1 which are known to increase cyclic AMP in neuroblastoma cells potentiated the acetylcholine-induced muscarinic hyperpolarization of the cells without changing the resting membrane potential. The potentiation caused by 2-chloroadenosine was further augmented by Ro 20-1724, a phosphodiesterase inhibitor. A direct intracellular pressure application of cyclic AMP potentiated the muscarinic hyperpolarization without changing the resting membrane potential. Morphine which inhibits adenylate cyclase antagonized 2-chloroadenosine-induced potentiation of the muscarinic hyperpolarization. These results suggest that changes in cyclic AMP level modulate the muscarinic response of neuroblastoma cells.
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PMID:Cyclic AMP-mediated potentiation of muscarinic hyperpolarization in neuroblastoma cells. 632 Sep 77

In addition to the mu- and delta-opioid receptors previously reported, the SH-SY5Y human neuroblastoma cell line has high levels of kappa 3 receptors, accounting for 40% of total opioid binding, as measured with [3H]-diprenorphine binding. Competition studies reveal binding profiles for all three receptor classes that are similar to those observed in brain membranes. Differentiation with retinoic acid increases the levels of opioid receptor binding in the cell line, with the largest elevations in kappa 3 binding. Fully 75% of the increased binding corresponds to kappa 3 sites, which represent 50% of total opioid receptor binding in differentiated cells. Morphine inhibits forskolin-stimulated cyclic AMP accumulation, and this effect is readily blocked by the mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Naloxone benzoylhydrazone, a kappa 3 agonist, inhibits forskolin-stimulated cyclic AMP accumulation more potently than morphine and is not reversed by CTAP. These studies indicate that SH-SY5Y cells contain high levels of functional kappa 3 receptors.
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PMID:Demonstration of kappa 3-opioid receptors in the SH-SY5Y human neuroblastoma cell line. 779 Aug 58

Mu and delta opiate receptor regulation by opiate agonists and antagonists was studied in the human neuroblastoma cell line SH-SY5Y. Morphine down-regulated both mu and delta receptors, but its effects on each subtype could be dissociated by use of specific antagonists. The selective mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Pen-Thr-NH2 (CTAP) blocked the down-regulation of mu, but not delta receptors. Conversely, the delta antagonist (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH([N,N-diallyl-Tyr1, Aib2,3]Leu- enkephalin)] ICI 174,864 blocked morphine-induced down-regulation of delta but not mu receptors. These selective antagonists also were studied alone for their effects on both receptors. CTAP alone at doses of 0.1 microM and higher up-regulated mu receptors. CTAP did not affect delta receptors at 0.3 microM or less, but it down-regulated them at doses of 1 microM or more, apparently due to its delta agonist activity at higher doses, which was reversed by ICI 174,864. ICI 174,864 alone also showed complex effects on the two subtypes, up-regulating both mu and delta sites. Its effects were most selective at a low dose (0.1 microM), which upregulated delta sites with minimal effects on mu sites. The nonselective antagonist naloxone provided a more robust upregulation (> 40%) of both mu and delta receptors than either selective antagonist alone or in combination. The mu-to-delta ratio (1.4 to 1) was not altered by differentiation of the cells with retinoic acid, which up-regulated both mu and delta receptors. Differentiation with the phorbol agent 12-O-tetradecanoyl-phorbol-13-acetate, however, up-regulated mu, but not delta receptors. The selective mu agonist Tyr-Pro-MePhe-D-Pro-NH2 (PL017) down-regulated mu receptors with a half-maximal effect at 180 nM, but was without effect on delta receptors at concentrations up to 10 microM. Conversely, the selective delta agonist Tyr-D-Pen-Gly-Phe-D-Pen([D-Pen2,5]-enkephalin) (DPDPE) potently down-regulated delta receptors, producing half-maximal decreases at 0.5 nM. At doses above those that reduced the maximum binding of [3H]pCl-DPDPE binding to the delta site, DPDPE also induced an apparent loss of affinity (increased Kd) at the delta site. It was without effect on mu receptors, however, at doses up to 10 microM. Thus, down-regulation of mu and delta receptors was homologous, because selective agonists down-regulated their respective receptors without effect on the heterologous opiate receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of mu and delta opiate receptors by morphine, selective agonists and antagonists and differentiating agents in SH-SY5Y human neuroblastoma cells. 793 56

Receptor interactions of morphine are reviewed, with particular attention given to a recently discovered opiate receptor, designated mu 3, with unique selectivity for morphine and certain other opiate alkaloids. Morphine, other opiate alkaloids and related analogs are known to bind to the classical delta, mu and kappa opioid receptor subtypes. Each of these subtypes also binds one or more of the endogenous opioid peptides with high affinity. Immunocytes have recently been found to contain a unique receptor for morphine, capable of binding morphine and certain other opiate alkaloids, but with essentially no or exceedingly low affinity for the naturally occurring endogenous opioid peptides or peptide analogs. This putative mu 3 (morphine/opiate alkaloid) receptor is present in invertebrate immunocytes as well as in human peripheral blood monocytes (macrophages). More recently this same receptor has been found in certain established macrophage cell lines and in human peripheral blood granulocytes. Finally, the same or closely related opiate alkaloid-selective (mu 3) receptor has been found to be present in a neuroblastoma and in a hybrid neural cell line. Studies indicate that in the immunocytes the receptor mediates inhibitory effects of morphine on cellular chemotaxis. While the functional coupling of this receptor in neurons is not known, it is postulated that the receptor may mediate effects of opiates on neuronal differentiation and cell division as well as neuronal transmission. Both for the immune system and the nervous system, the mu 3 receptor may constitute a major site of action for putative endogenous morphine or morphine-like substances. This receptor system also provides an additional pharmacological site of action for exogenously administered opiate alkaloid drugs. The mu 3 receptor is proposed to be an important neuro-immune link. This system is likely to play a significant role in a variety of responses involving the immune system, including the response of the organism to stress, infection and malignant transformation.
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PMID:Morphine receptors in immunocytes and neurons. 795 30

The human neuroblastoma cell line SH-SY5Y was used to demonstrate morphine-induced down-regulation and naloxone-induced up-regulation of opiate receptors in a mu receptor containing neuronally derived preparation capable of desensitization to morphine. Chronic exposure to morphine decreased the number but not the affinity of mu opiate receptors in SH-SY5Y cells. Differentiation of the cells with retinoic acid or with the phorbol agent TPA (12-O-tetradecanoyl-phorbol-13-acetate) increased the number of mu receptors. Morphine-induced down-regulation, however, was observed in the absence of differentiation as well as after differentiation with retinoic acid or TPA. The decrease in the number of receptors was related to time of exposure, with a half-maximum disappearance time (T1/2) of about 3 hr during the initial phase. The receptor decrease was near maximum at 24 hr with no further significant change up to 72 hr. The loss of [3H] DAMGO ([3H]Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) binding was also dose-dependent, with reductions occurring at 0.3, 1 and 10 microM. The loss of receptors was dependent on temperature, with reductions at 37 but not 23 degrees C. The down-regulation was blocked by naloxone and the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D(-Trp-)Orn-Thr-Pen-Thr-NH2), but not by the delta antagonist ICI 174864 ([N,N-diallyl-Tyr1,Aib2,3]Leu-enkephalin). Cholinergic ([3H]quinclidinyl benzilate) binding was not affected by the morphine treatment, indicating that the down-regulation was homologous for opiate receptors. In SH-SY5Y cells, unlike other cell models, the opiate antagonist naloxone upregulated mu receptors by more than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mu opiate receptor down-regulation by morphine and up-regulation by naloxone in SH-SY5Y human neuroblastoma cells. 809 44

Human neuroblastoma SK-N-SH cells, which contain both mu- and delta-opioid receptors, were grown under conditions that provided a mu:delta ratio of 1.5:1. Both receptors were down-regulated after 72 hr of exposure to 100 nM etorphine. Selective down-regulation was demonstrated using selective opioid agonists; the mu agonist Tyr-D-Ala2-Gly-(Me)Phe4-Gly-ol down-regulated mu- but not delta-opioid receptors, whereas prolonged exposure to the selective delta agonist D-Pen2,D-Pen5-enkephalin resulted in delta- but not mu-opioid receptor down-regulation. Morphine, which binds mu- as well as delta-opioid receptors, down-regulated both receptor subtypes. NG108-15 cells, which contain delta receptors exclusively, were also tested. NG108-15 cells did not exhibit delta-opioid receptor down-regulation when exposed to morphine. The discrepancy between the effect of chronic morphine treatment on delta receptors in SK-N-SH cells and in NG108-15 cells raised the question of whether the coexistence of mu receptors in the former allowed morphine to down-regulate delta receptors. The role of mu-opioid receptors in morphine-induced delta receptor down-regulation was studied by using the irreversible mu antagonist beta-funaltrexamine. Pretreatment of SK-N-SH cells with beta-funaltrexamine prevented down-regulation of delta receptors in response to chronic exposure to morphine but did not affect down-regulation of delta receptors in response to D-Pen2,D-Pen5-enkephalin. The experimental data indicate that morphine-induced delta-opioid receptor down-regulation is dependent on the presence of functional mu receptors in the same cell.
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PMID:Selective and interactive down-regulation of mu- and delta-opioid receptors in human neuroblastoma SK-N-SH cells. 839 99

1. The agonist action of morphine on membranes prepared from human neuroblastoma SH-SY5Y cells was measured by an increase in the binding of the GTP analogue [35S]-GTPgammaS. Morphine increased the binding of [35S]-GTPgammaS to SH-SY5Y cell membranes by 30 fmol mg(-1) protein with an EC50 value of 76 +/- 10 nM. 2. Incubation of SH-SY5Y cells with 10 microM morphine for 48 h caused a tolerance to morphine manifested by a 2.5 fold shift to the right in the EC50 value with a 31 +/- 6% decrease in the maximum stimulation of [35S]-GTPgammaS binding. The response caused by the partial agonist pentazocine was reduced to a greater extent. 3. Chronic treatment of the cells with the more efficacious mu-ligand [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO, 10 microM) for 48 h afforded a greater effect than treatment with morphine. The maximal agonist effect of morphine was reduced to 58.9 +/- 6% of that seen in control cells while the maximal effect of DAMGO was reduced to 62.8 +/- 4%. There was a complete loss of agonist activity for pentazocine. 4. The development of tolerance was complete within 24 h and was blocked by naloxone and by the nonselective protein kinase inhibitor H7, but not by the putative beta-adrenoceptor kinase (beta-ARK) inhibitor suramin. 5. The observed tolerance effect was accompanied by a down-regulation of mu-opioid receptors determined by a decrease in the maximal binding capacity for the opioid antagonist [3H]-diprenorphine of 66 +/- 4%, but with no change in binding affinity. Binding of the agonist [3H]-DAMGO was similarly reduced. 6. The modulation of [35S]-GTPgammaS binding in SH-SY5Y cell membranes by opioids provides a simple method for the study of opioid tolerance at a site early in the signal transduction cascade.
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PMID:Tolerance to mu-opioid agonists in human neuroblastoma SH-SY5Y cells as determined by changes in guanosine-5'-O-(3-[35S]-thio)triphosphate binding. 925 23

N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12), a nitric oxide donor, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite (ONOO-), and peroxynitrite induced cell death accompanied by DNA fragmentation in human neuroblastoma SH-SY5Y cell cultures. Morphine prevented the cell death induced by SIN-1 or peroxynitrite, but not that induced by NOC12. The protective effect of morphine was concentration-dependent (10-100 microM), but was not antagonized by naloxone. The selective ligands for opioid receptor subtypes, [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO, micro-opioid receptor agonist), [D-Pen2,5]enkephalin (DPDPE, delta-opioid receptor agonist) and trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benze neacetamide (U-50488, kappa-opioid receptor agonist) even at the concentration of 100 microM did not prevent the cell death induced by SIN-1. From measurement of the absorbance spectrum of peroxynitrite, the decomposition of peroxynitrite in 0.25 M potassium phosphate buffer (pH 7.4) was very rapid and complete within seconds. However, the absorbance was very stable in the presence of morphine. In addition, morphine inhibited peroxynitrite-induced nitration of tyrosine in a concentration-dependent manner. These results indicate that morphine rapidly reacts with peroxynitrite. The present study showed that morphine prevented peroxynitrite-induced cell death through its direct scavenging action, suggesting that morphine can protect cells against damage caused by peroxynitrite.
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PMID:Morphine prevents peroxynitrite-induced death of human neuroblastoma SH-SY5Y cells through a direct scavenging action. 1039 28

The recently discovered endogenous peptide orphanin FQ/nociceptin (OFQ/N) activates the opioid receptor-like 1 (ORL1) receptor and produces diverse effects on pain perception. In addition to producing spinal analgesia, OFQ/N also exhibits an 'anti-opioid activity' against functional (supraspinal analgesia) and behavioral (conditioned place preference and withdrawal) properties of morphine. One manifestation of the behavioral changes resulting from chronic use of morphine is the upregulation of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis), which contributes to the dramatic increases in catecholamine release in the target regions of the locus coeruleus (LC) and the ventral tegmental area (VTA). The present study sought to determine the molecular mechanism(s) by which OFQ/N modulates the chronic actions of morphine by utilizing human neuroblastoma cell lines [BE(2)-C and SH-SY5Y] that endogenously express TH, and mu and ORL1 receptors. Activation of mu or ORL1 receptors in these cells in turn activates extracellular signal-regulated protein kinases (ERKs), ERK1 and ERK2. Chronic activation of mu, but not ORL1, receptors upregulated TH levels in these cells as previously reported in rat brain. Morphine-induced TH upregulation was blocked upon inclusion of a MEK-1 (mitogen-activated protein kinase kinase-1) inhibitor (PD98059), confirming the role for ERKs in this adaptive response to morphine. Inclusion of OFQ/N during chronic morphine exposure also blocked morphine-induced TH upregulation. Furthermore, chronic OFQ/N exposure increased levels of the TH gene repressor, Oct-2, irrespective of the presence or absence of morphine. This report suggests a potential role for Oct-2 in mediating the anti-opioid actions of OFQ/N against the behavioral manifestations resulting from chronic use of morphine.
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PMID:Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation. 1239 6

A sensitive quantitative-competitive reverse transcriptase-polymerase chain reaction method was developed to measure micro-opioid receptor (MOR) mRNA expression in SHSY-5Y neuroblastoma cells. Differentiation of SHSY-5Y cells with either retinoic acid (RA) or 12-o-tetradecanoyl-phorbol-13-acetate (TPA) significantly increased MOR mRNA levels. Morphine treatment (10 microM) for 24 h decreased MOR mRNA levels in control, as well as RA- and TPA-differentiated cells. In contrast, chronic exposure to the opioid peptides endomorphin-1 or endomorphin-2 significantly increased MOR mRNA levels in undifferentiated and RA-differentiated cells. An opioid antagonist, naloxone, reversed the morphine and endomorphin-1 and -2 effects on MOR mRNA levels in undifferentiated SHSY-5Y cells, but naloxone had differential reversing effects on the agonists' regulation of MOR mRNA in RA- or TPA-differentiated cells. To investigate whether the changes in MOR mRNA expression paralleled changes in MOR receptor function, intracellular cAMP accumulation in SHSY-5Y cells was measured. After chronic treatment with morphine, forskolin-induced cAMP levels in SHSY-5Y cells were significantly higher than those of untreated control cells. In contrast, forskolin-induced cAMP accumulation levels were lower in cells treated with endomorphin-1 or -2 than in untreated control cells. Together, our studies indicate that the opioid alkaloid morphine and the opioid peptides endomorphin-1 and -2 differentially regulate MOR mRNA expression and MOR function in SHSY-5Y cells.
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PMID:Morphine and endomorphins differentially regulate micro-opioid receptor mRNA in SHSY-5Y human neuroblastoma cells. 1275 18


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