scholarly journals Cellular tolerance at the μ-opioid receptor is phosphorylation dependent

2018 ◽  
Author(s):  
Seksiri Arttamangkul ◽  
Daniel A Heinze ◽  
James R Bunzow ◽  
Xianqiang Song ◽  
John T Williams
Keyword(s):  
Opioid Receptor ◽  
Potassium Conductance ◽  
Wild Type ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
C Terminus ◽  
Μ Opioid Receptor ◽  
Chronic Morphine Treatment

AbstractThe role of phosphorylation of the μ-opioid receptor (MOR) in desensitization, internalization and long-term tolerance was examined in locus coeruleus (LC) neurons. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in a MOR knockout rat. Both expressed receptors acutely activate potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, displayed signs of tolerance after chronic morphine treatment. There was however a loss of agonist-induced desensitization and internalization in experiments with the TPD receptors. In addition the development of tolerance was not observed in the TPD receptors following chronic morphine treatment. The results indicate a key role of C-terminal phosphorylation in the expression of acute desensitization, trafficking and long-term tolerance to morphine.

scholarly journals Cellular tolerance at the µ-opioid receptor is phosphorylation dependent

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Seksiri Arttamangkul ◽  
Daniel A Heinz ◽  
James R Bunzow ◽  
Xianqiang Song ◽  
John T Williams
Keyword(s):  
Opioid Receptor ◽  
Potassium Conductance ◽  
Cellular Level ◽  
Wild Type ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
C Terminus ◽  
Chronic Morphine Treatment ◽  
Cellular Tolerance

Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus coeruleus neurons in a MOR knockout rat. Both receptors activated potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, acutely desensitized, internalized and, after chronic morphine treatment, displayed signs of tolerance. However, TPD receptors did not desensitize or internalize with agonist treatment. In addition the TPD receptors did not develop cellular tolerance following chronic morphine treatment. Thus C-terminal phosphorylation is necessary for the expression of acute desensitization, trafficking and one sign of long-term tolerance to morphine at the cellular level.

scholarly journals Long-Term Morphine Treatment Decreases the Association of μ-Opioid Receptor (MOR1) mRNA with Polysomes through miRNA23b

2009 ◽  
Vol 75 (4) ◽  
pp. 744-750 ◽  
Author(s):  
Qifang Wu ◽  
Lei Zhang ◽  
Ping-Yee Law ◽  
Li-Na Wei ◽  
Horace H. Loh
Keyword(s):  
Opioid Receptor ◽  
Morphine Treatment ◽  
Μ Opioid Receptor

Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in activity after chronic morphine treatment

1997 ◽  
Vol 746 (1-2) ◽  
pp. 10-18 ◽  
Author(s):  
Dana E Selley ◽  
Eric J Nestler ◽  
Christopher S Breivogel ◽  
Steven R Childers
Keyword(s):  
Locus Coeruleus ◽  
G Proteins ◽  
Opioid Receptor ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment

Preconditioning with morphine protects hippocampal CA1 neurons from ischemia–reperfusion injury via activation of the mTOR pathway

2018 ◽  
Vol 96 (1) ◽  
pp. 80-87 ◽  
Author(s):  
Maedeh Arabian ◽  
Nahid Aboutaleb ◽  
Mansoureh Soleimani ◽  
Marjan Ajami ◽  
Rouhollah Habibey ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Mtor Pathway ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Sod Activity ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Chronic Morphine Treatment

The signaling pathway of chronic morphine treatment to prevent neuronal damage following transient cerebral ischemia is not clear. In this study, we examined the role of mammalian target of rapamycin (mTOR) to identify the neuroprotective effects of chronic morphine preconditioning on the hippocampus following ischemia–reperfusion (I/R) injury. Morphine was administered for 5 days, twice a day, before inducing I/R injury. The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. The passive avoidance test was used to evaluate memory performance. Neuronal density and apoptosis were measured in the CA1 region, 72 h after I/R injury. The expressions of mTOR and phosphorylated mTOR (p-mTOR), as well as superoxide dismutase (SOD) activity were determined 24 h after I/R injury. Chronic morphine treatment attenuated apoptosis and neuronal loss in the hippocampus after I/R injury, which led to improvement in memory (P < 0.05 vs. untreated I/R) and increase in the expression of p-mTOR (P < 0.05 vs. untreated I/R) and SOD activity (P < 0.05 vs. untreated I/R) in the hippocampus. Pretreatment with rapamycin abolished all the above-mentioned protective effects. These results describe novel findings whereby chronic morphine preconditioning in hippocampal CA1 neurons is mediated by the mTOR pathway, and through increased phosphorylation of mTOR can alleviate oxidative stress and apoptosis, and eventually protect the hippocampus from I/R injury.

Role of Adrenal Cortical Activation in the Immunosuppressive Effects of Chronic Morphine Treatment*

Endocrinology ◽  
1991 ◽  
Vol 128 (6) ◽  
pp. 3253-3258 ◽  
Author(s):  
H. U. BRYANT ◽  
E. W. BERNTON ◽  
J. R. KENNER ◽  
J. W. HOLADAY
Keyword(s):  
Cortical Activation ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment
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