Abstract：
:Desensitization of the micro-opioid receptor (MOR) has been implicated as an important regulatory process in the development of tolerance to opiates. Monitoring the release of intracellular Ca(2+) ([Ca(2+)](i)), we reported that [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO)-induced receptor desensitization requires receptor phosphorylation and recruitment of beta-arrestins (betaArrs), while morphine-induced receptor desensitization does not. In current studies, we established that morphine-induced MOR desensitization is protein kinase C (PKC)-dependent. By using RNA interference techniques and subtype specific inhibitors, PKCepsilon was shown to be the PKC subtype activated by morphine and the subtype responsible for morphine-induced desensitization. In contrast, DAMGO did not increase PKCepsilon activity and DAMGO-induced MOR desensitization was not affected by modulating PKCepsilon activity. Among the various proteins within the receptor signaling complex, Galphai2 was phosphorylated by morphine-activated PKCepsilon. Moreover, mutating three putative PKC phosphorylation sites, Ser(44), Ser(144) and Ser(302) on Galphai2 to Ala attenuated morphine-induced, but not DAMGO-induced desensitization. In addition, pretreatment with morphine desensitized cannabinoid receptor CB1 agonist WIN 55212-2-induced [Ca(2+)](i) release, and this desensitization could be reversed by pretreating the cells with PKCepsilon inhibitor or overexpressing Galphai2 with the putative PKC phosphorylation sites mutated. Thus, depending on the agonist, activation of MOR could lead to heterologous desensitization and probable crosstalk between MOR and other Galphai-coupled receptors, such as the CB1.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Chu J,Zheng H,Zhang Y,Loh HH,Law PYdoi
10.1016/j.cellsig.2009.12.003subject
Has Abstractpub_date
2010-04-01 00:00:00pages
684-96issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(09)00386-6journal_volume
22pub_type
杂志文章abstract：:Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact are not understood. Here we delineate how Akt and Rac1 pathways signal to increa...
journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.04.003
更新日期：2011-08-01 00:00:00
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journal_title：Cellular signalling
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更新日期：2013-12-01 00:00:00
abstract：:The present study was undertaken to investigate whether purified ras proteins can affect the activity of polyphosphoinositide specific phospholipase C in a cell-free membrane system. For this purpose we used homogenous preparations of the proto-oncogenic (H-ras(gly 12)) and the oncogenic (H-ras(val 12)) forms of the h...
journal_title：Cellular signalling
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journal_title：Cellular signalling
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abstract：:Regulation by unsaturated fatty acids of glucocorticoid-sensitive gene transcription was studied in HeLa cells transiently transfected with a mouse mammary tumour virus-luciferase reporter gene. Arachidonic acid and docosahexaenoic acid by themselves had no effect on basal levels of luciferase expression. However, the...
journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：1995-05-01 00:00:00
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.06.011
更新日期：2012-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.06.005
更新日期：2013-10-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.04.003
更新日期：2008-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(03)00099-8
更新日期：2003-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.11.016
更新日期：2011-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.05.017
更新日期：2006-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.08.006
更新日期：2008-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(96)00073-3
更新日期：1996-09-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.03.006
更新日期：2005-12-01 00:00:00
abstract：:Ethanol, in millimolar concentrations, significantly modifies different transductive systems in human lymphocyte cultures. In particular, the presence of alcohol in the medium more than doubles the [Ca2+]i (from 70-90 to 200-250 nM), increasing Ca2+ fluxes from outside, and inhibits the active transport carried out by...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(93)90065-t
更新日期：1993-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.05.015
更新日期：2006-04-01 00:00:00
abstract：:This article has been withdrawn at the request of the Editors. The Publisher apologises for any inconvenience that this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.05.011
更新日期：2009-03-27 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(89)90023-5
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.10.008
更新日期：2005-05-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.04.009
更新日期：2017-07-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109904
更新日期：2020-12-25 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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更新日期：1998-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.09.019
更新日期：2014-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.01.005
更新日期：2019-05-01 00:00:00
abstract：BACKGROUND:MicroRNAs (miRNAs) are key regulators of many cellular pathways. However, the picture for components or regulators involved in the process of miRNA biogenesis and function remains to be further elucidated. Early growth response gene 1 (Egr1) has long been considered as tumor suppressor and transcriptional fa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.02.016
更新日期：2015-06-01 00:00:00
abstract：:Cd(2+) exposure increases the risk of cancer in humans and animals. In this report, we have studied the effect of Cd(2+) on signal transduction and Ca(2+) mobilization in murine macrophages. At micromolar concentrations, Cd(2+) significantly increased cell division as judged by [3H]thymidine uptake and cell counts. Cd...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00268-6
更新日期：2002-04-01 00:00:00
abstract：:Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA s...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109696
更新日期：2020-09-01 00:00:00
