scholarly journals Heteromerization Modulates mu Opioid Receptor Functional Properties in vivo

2018 ◽  
Vol 9 ◽  
Author(s):  
Muzeyyen Ugur ◽  
Lyes Derouiche ◽  
Dominique Massotte
Keyword(s):  
Opioid Receptor ◽  
Functional Properties ◽  
Mu Opioid Receptor ◽  
Mu Opioid

Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma

Life Sciences ◽  
2021 ◽  
Vol 278 ◽  
pp. 119541
Author(s):  
Aysegul Gorur ◽  
Miguel Patiño ◽  
Hideaki Takahashi ◽  
German Corrales ◽  
Curtis R. Pickering ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Opioid Receptor ◽  
Receptor Activation ◽  
Mu Opioid Receptor ◽  
Mu Opioid

scholarly journals 6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects

2021 ◽  
Author(s):  
Nicholas S. Akins ◽  
Nisha Mishra ◽  
Hannah M. Harris ◽  
Narendar Dudhipala ◽  
Seong Jong Kim ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Activity ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists

Analgesia is commonly mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. Recently, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold <i>via</i> an ester linker. <i>In vitro</i> studies showed that some of these compounds have dual agonism on kappa and mu opioid receptors, while some have triple agonism on kappa, mu, and delta. <i>In vivo </i>studies on the lead dual kappa and mu opioid receptor agonist, compound <b>10</b>, showed that it<b> </b>produced analgesic activity while avoiding anxiogenic effects in murine models, thus providing further strong evidence for the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor

2007 ◽  
Vol 0 (0) ◽  
pp. 070630082917007-??? ◽  
Author(s):  
Thomas Kroslak ◽  
K. Steven LaForge ◽  
Robert J. Gianotti ◽  
Ann Ho ◽  
David A. Nielsen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Opioid Receptor ◽  
Functional Properties ◽  
Mu Opioid Receptor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Mu Opioid

scholarly journals In Vitro Effects of Ligand Bias on Primate Mu Opioid Receptor Downstream Signaling

2020 ◽  
Vol 21 (11) ◽  
pp. 3999
Author(s):  
Xiao Zhang ◽  
Shaurita D. Hutchins ◽  
Bruce E. Blough ◽  
Eric J. Vallender
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Luciferase Reporter ◽  
Response Curves ◽  
Mu Opioid ◽  
Biased Agonism ◽  
Downstream Signaling ◽  
Ligand Bias

Interest has emerged in biased agonists at the mu opioid receptor (MOR) as a possible means for maintaining potent analgesis with reduced side effect profiles. While approaches measuring in vitro biased agonism are used in the development of these compounds, their therapeutic utility will ultimately be determined by in vivo functional effects. Nonhuman primates (NHPs) are the most translational model for evaluating the behavioral effects of candidate medications, but biased signaling of these drugs at NHP MOR receptors has been unstudied. The goal of the current work was to characterize MOR ligand bias in rhesus macaques, focusing on agonists that have previously been reported to show different patterns of biased agonism in rodents and humans. Downstream signaling pathways that responded to MOR activation were identified using a luciferase reporter array. Concentration-response curves for specific pathways (cAMP, NF-ĸB, MAPK/JNK) were generated using six agonists previously reported to differ in terms of signaling bias at rodent and human MORs. Using DAMGO as a reference ligand, relative cAMP, NF-ĸB and MAPK/JNK signaling by morphine, endomorphin-1, and TRV130 were found to be comparable between species. Further, the bias patterns of across ligands for NF-ĸB and MAPK/JNK were largely similar between species. There was a high degree of concordance between rhesus macaque and human MOR receptor signaling bias for all agonists tested, further demonstrating their utility for future translational behavioral studies.

scholarly journals Evidence of Endogenous Mu Opioid Receptor Regulation by Epigenetic Control of the Promoters

2007 ◽  
Vol 27 (13) ◽  
pp. 4720-4736 ◽  
Author(s):  
Cheol Kyu Hwang ◽  
Kyu Young Song ◽  
Chun Sung Kim ◽  
Hack Sun Choi ◽  
Xiao-Hong Guo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Opioid Receptor ◽  
Promoter Region ◽  
Histone Deacetylase Inhibitors ◽  
Mu Opioid Receptor ◽  
Histone Deacetylation ◽  
Epigenetic Mechanism ◽  
Proximal Promoter ◽  
Mu Opioid

ABSTRACT The pharmacological effect of morphine as a painkiller is mediated mainly via the mu opioid receptor (MOR) and is dependent on the number of MORs in the cell surface membrane. While several studies have reported that the MOR gene is regulated by various cis- and trans-acting factors, many questions remain unanswered regarding in vivo regulation. The present study shows that epigenetic silencing and activation of the MOR gene are achieved through coordinated regulation at both the histone and DNA levels. In P19 mouse embryonal carcinoma cells, expression of the MOR was greatly increased after neuronal differentiation. MOR expression could also be induced by a demethylating agent (5′-aza-2′-deoxycytidine) or histone deacetylase inhibitors in the P19 cells, suggesting involvement of DNA methylation and histone deacetylation for MOR gene silencing. Analysis of CpG DNA methylation revealed that the proximal promoter region was unmethylated in differentiated cells compared to its hypermethylation in undifferentiated cells. In contrast, the methylation of other regions was not changed in either cell type. Similar methylation patterns were observed in the mouse brain. In vitro methylation of the MOR promoters suppressed promoter activity in the reporter assay. Upon differentiation, the in vivo interaction of MeCP2 was reduced in the MOR promoter region, coincident with histone modifications that are relevant to active transcription. When MeCP2 was disrupted using MeCP2 small interfering RNA, the endogenous MOR gene was increased. These data suggest that DNA methylation is closely linked to the MeCP2-mediated chromatin structure of the MOR gene. Here, we propose that an epigenetic mechanism consisting of DNA methylation and chromatin modification underlies the cell stage-specific mechanism of MOR gene expression.

scholarly journals In Vitro and In Vivo Pharmacological Comparison of Mu‐Opioid Receptor Activity of the Kratom ( Mitragyna speciosa ) Alkaloid Mitragynine and its Metabolite 7‐Hydroxymitragynine

2021 ◽  
Vol 17 (S9) ◽  
Author(s):  
Maria P Guerrero Calvache ◽  
Samuel Obeng ◽  
Francisco Leon ◽  
Lea R Gamez‐Jimenez ◽  
Avi Patel ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Receptor Activity ◽  
Mu Opioid ◽  
Mitragyna Speciosa

In vitro and in vivo activity of cyclopeptide Dmt-c[ d -Lys-Phe-Asp]NH 2 , a mu opioid receptor agonist biased toward β-arrestin

Peptides ◽  
2018 ◽  
Vol 105 ◽  
pp. 51-57 ◽  
Author(s):  
Katarzyna Gach-Janczak ◽  
Justyna Piekielna-Ciesielska ◽  
Anna Adamska-Bartłomiejczyk ◽  
Karol Wtorek ◽  
Federica Ferrari ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

scholarly journals Reduced mu opioid receptor availability in schizophrenia revealed with [11C]-carfentanil positron emission tomographic Imaging

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Abhishekh H. Ashok ◽  
Jim Myers ◽  
Tiago Reis Marques ◽  
Eugenii A. Rabiner ◽  
Oliver D. Howes
Keyword(s):  
Opioid Receptor ◽  
Negative Symptoms ◽  
Molecular Mechanisms ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Reward Function ◽  
Positron Emission ◽  
Global Increase ◽  
Hedonic Processing

Abstract Negative symptoms, such as amotivation and anhedonia, are a major cause of functional impairment in schizophrenia. There are currently no licensed treatments for negative symptoms, highlighting the need to understand the molecular mechanisms underlying them. Mu-opioid receptors (MOR) in the striatum play a key role in hedonic processing and reward function and are reduced post-mortem in schizophrenia. However, it is unknown if mu-opioid receptor availability is altered in-vivo or related to negative symptoms in schizophrenia. Using [11 C]-carfentanil positron emission tomography (PET) scans in 19 schizophrenia patients and 20 age-matched healthy controls, here we show a significantly lower MOR availability in patients with schizophrenia in the striatum (Cohen’s d = 0.7), and the hedonic network. In addition, we report a marked global increase in inter-regional covariance of MOR availability in schizophrenia, largely due to increased cortical-subcortical covariance.

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