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)

mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity.
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PMID:Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells. 127 57

One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism.
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PMID:Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA. 283 57

In mice ascorbate, when co-administered with morphine, suppresses the development of tolerance and physical dependence on the drug, without significantly affecting its analgesic properties as inferred from unaltered ED50 values. The duration of morphine-induced analgesia, however, is progressively reduced with an increase in the amounts of ascorbate. Ascorbate at 1g/kg body weight does not alter the pH of blood, and has no effect on the levels of lipid-peroxides in blood and brain. Studies presented in this paper suggest the potential use of ascorbate in the prevention of development of tolerance in therapeutic applications of narcotics as analgesics. Cultured Neuroblastoma X Glioma hybrid cells (NG 108-15) respond to opiates in two different ways. The rapid receptor mediated inhibition of adenylate cyclase is followed by a long-lived compensatory increase in its activity (1-4). In a recent report (5) we have shown that ascorbate suppresses the delayed etorphine-induced compensatory increase in cAMP levels in NG 108-15 cells without affecting the short-term inhibitory response of cells to the drug. It has been suggested that while the former may be the basis of narcotic dependence and tolerance, the latter is responsible for the analgesic effect. These observations, based on a model system, prompted us to examine the effect of ascorbate on the pharmacological properties of morphine at the organismal level.
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PMID:Megadoses of vitamin C prevent the development of tolerance and physical dependence on morphine in mice. 668 37

Chronic administration of narcotic mu opioid agonists results in tolerance and dependence. We propose that agonist stimulation causes a gradual conversion of mu receptors to a constitutively active state (mu*) as a key step in tolerance and physical dependence. We provide evidence in support of the existence of mu* in human neuroblastoma cells, SH-SY5Y, and mu* upregulation during morphine treatment. Naloxone blocked mu* activity, acting as an antagonist with negative intrinsic activity which accounts for its high potency in eliciting withdrawal. In contrast, the mu selective antagonist CTAP did not affect mu* activity but inhibited naloxone's effect. The protein kinase inhibitor H7 was found to suppress mu* formation, suggesting that mu* is phosphorylated. In a model of acute morphine tolerance/dependence in mice, H7 prevented naloxone induced withdrawal jumping and reversed morphine (antinociceptive) tolerance. CTAP caused only mild withdrawal and attenuated naloxone induced withdrawal, as predicted for an antagonist without negative activity. These results support a role for constitutive mu receptor activation in narcotic tolerance and dependence, affording potential separation of acute and chronic narcotic effects.
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PMID:Constitutive mu opioid receptor activation as a regulatory mechanism underlying narcotic tolerance and dependence. 751 10

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.
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PMID:Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. 1109