BioAssay record AID 391164 submitted by ChEMBL: Displacement of [3H]DAMGO from rat mu opioid receptor expressed in mouse HN9.10 cell membrane by liquid scintillation counting.
BioAssay record AID 349684 submitted by ChEMBL: Displacement of [3H]diprenorphine from N-terminal HA epitope-tagged rat mu opioid receptor expressed in HEK293 cells by scintillation counting.
At present, divergent views exist concerning the extent to which either opioid receptor desensitization or adenylate cyclase superactivation contribute to the development of tolerance to morphine. The receptor activity versus endocytosis (RAVE) model proposes that morphine may induce adenylate cyclase superactivation to a greater extent than other opioids, which in turn exacerbates the development of tolerance (Whistler et al, 1999; Finn and Whistler, 2001). In contrast, studies using mice lacking β‐arrestin‐2 show that opioid receptor desensitization directly contributes to tolerance and that tolerance and adenylyl cyclase superactivation are two dissociable phenomena (Bohn et al, 1999, 2000). Here, we propose that morphine is unique in that it promotes terminal opioid receptor desensitization by inducing a sustained phosphorylation of Ser375. Morphine‐desensitized receptors remain at the plasma membrane in a Ser375‐phosphorylated state for prolonged periods and are not able to enter ...
RNA Biol. 2013 Feb;10(2):256-66. doi: 10.4161/rna.23022. Epub 2013 Jan 25. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Govt
The µ-opioid receptor is the primary target structure of most opioid analgesics and thus responsible for the predominant part of their wanted and unwanted effects. Carriers of the frequent genetic µ-opioid receptor variant N40D (allelic frequency 8.2 - 17 %), coded by the single nucleotide polymorphism A|G at position 118 of the µ-opioid receptor coding gene OPRM1 (OPRM1 118A|G SNP), suffer from a decreased opioid potency and from a higher need of opioid analgesics to reach adequate analgesia. The aim of the present work was to identify the mechanism by which the OPRM1 118A|G SNP decreases the opioid potency and to quantify its effects on the analgesic potency and therapeutic range of opioid analgesics. To elucidate the consequences of the OPRM1 118A|G SNP for the effects of opioid analgesics, brain regions of healthy homozygous carriers of the OPRM1 118A|G SNP were identified by means of functional magnetic resonace imaging (fMRI), where the variant alters the response to opioid analgesics after
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mu Opioid Receptors: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Background Opioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development...
Mechling AE, Arefin T, Lee H-L, Bienert T, Reisert M, Ben Hamida S, Darcq E, Ehrlich A, Gaveriaux-Ruff C, Parent MJ et al.. 2016. Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.. Proc Natl Acad Sci U S A. 113(41):11603-11608. ...
Mechling AE, Arefin T, Lee H-L, Bienert T, Reisert M, Ben Hamida S, Darcq E, Ehrlich A, Gaveriaux-Ruff C, Parent MJ et al.. 2016. Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.. Proc Natl Acad Sci U S A. 113(41):11603-11608. ...
Background: Microglia activation contributes to chronic pain and to the adverse effects of opiate use such as analgesic tolerance and opioid-induced hyperalgesia. Both mu opioid receptor (MOR) encoded by Oprm1/OPRM1 gene and toll like receptor 4 (TLR4) have been reported to mediate these morphine effects and a current question is whether microglia express the Oprm1 transcript and MOR protein. The aim of this study was to characterize Oprm1-MOR expression in naive murine and human microglia, combining transcriptomics datasets previously published by other groups with our own imaging study using the Cx3cr1-eGFP-MOR-mCherry reporter mouse line.Methods: We analyzed microglial Oprm1/OPRM1 expression obtained from transcriptomics datasets, focusing on ex vivo studies from adult wild-type animals and adult post-mortem human cerebral cortex. Oprm1, as well as co-regulated gene sets were examined. The expression of MOR in microglia was also investigated using our novel fluorescent Cx3cr1-eGFP-MOR-mcherry
Hypoxia adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of hypoxia in which they may begin to die when oxygen supply is reduced or completely eliminated. Opioid receptor agonists have been shown to elicit several central nervous system effects, mediated via G protein-coupled receptors. The aim of this study was to study the effect of hypoxia on G protein coupled receptor gene expression using mu opioid receptor as a case study in cortical neuronal B50 cell lines in culture. The B50 cells were cultured in normoxia (21% O2; 5% CO2) and hypoxia (5% O2; 5% CO2), and were treated with opioid agonists to determine their effects on hypoxia-induced changes. Three opioid agonists {DAMGO(μ), DSLET(δ) and ICI--199,441(κ)}, were administered to the cells as treatment for 48 h after 48 h of initial culture for a total of 96 h of culture in hypoxic conditions at concentrations of 10, 50 and 100 μM. The levels of ...
Agonists targeting MOR are effective analgesics, but their clinical use is hindered by side effects, including tolerance and addiction. KOR agonists also produce analgesia, but clinical use of these compounds has remained minimal due to aversive properties in humans. The µ-opioid receptor (MOR) agonists, morphine and fentanyl, both activate c-Jun N-terminal kinase (JNK), which is required for spinally-mediated morphine acute analgesic tolerance, whereas acute analgesic tolerance to fentanyl is blocked by G protein-coupled receptor kinase 3 (GRK3) gene deletion. Similarly, the κ-opioid receptor (KOR) collateral antagonist, norBNI, stimulates phosphorylation of JNK, and JNK1 is specifically required for norBNIs long duration of antagonism. The durations of action of a broad range of KOR antagonists, including norBNI, positively correlate with the ability of the antagonist to activate JNK1 (Melief et al., 2011), whereas there is no correlation between duration of antagonist action and drug ...
The original description of the two endomorphins revealed that both compounds had a profound mu selectivity (Zadina et al., 1997). In this initial study both endomorphins competed mubinding over 1000-fold more potently than either delta orkappa1 receptors (Zadina et al., 1997). In the current studies, the two endomorphins also displayed very poor affinities for delta and kappa1receptors and high affinity for both mu receptor subtypes. Most opioids label mu1 receptors more potently than mu2 sites and the same trend was seen with the endomorphins, which displayed a 5- to 10-fold greater affinity in the mu1 binding assay. The high affinity of the two endomorphins for mu receptors was confirmed in competition studies against the cloned mu receptor MOR-1.. The initial study exploring the selectivity of the compounds did not examine kappa3 binding. We found that the endomorphins also competed kappa3 receptors moderately well, lowering binding with Ki values between 20 and 30 nM. Although the ...
We demonstrated that endocytosis-inducing agonists DAMGO and fentanyl enhanced morphine-induced MOR internalization of dorsal horn neurons in rats. We reproduced the remarkable, but previously somewhat controversial, effect of DAMGO to facilitate morphine-induced endocytosis reported by He et al. 14 and further showed that fentanyl, a clinically used opioid with internalization-inducing potency, has a similar effect on MOR internalization in vivo . More importantly, concomitant with the enhancement of MOR endocytosis, we observed that the acute analgesic effect of morphine evaluated by the HP test was greatly potentiated by coadministration of these agonists. As described in the Results, the increase in analgesia was not detected in TF test, the method used in the previous report.14 Probably because of the longer cutoff latency, i.e. , broader range in analgesic extent of the HP test, we were able to find the analgesic potentiation, although contribution of the difference in mechanism between ...
The endomorphins are a group of endogenous opioid peptides consisting of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2). They are tetrapeptides with the highest known affinity and selectivity for the μ-opioid receptor. Endomorphin-1 is found in the nucleus of the solitary tract, the periventricular hypothalamus, and the dorsomedial hypothalamus, where it is found within histaminergic neurons and may regulate sedative and arousal behaviors. It is assumed that endomorphins are the cleavage products of a larger precursor, but this polypeptide or protein has not yet been identified. In rats similarly potent dosages of synthetic endomorphin and morphine produced comparable amounts of pain relief. However, the rats receiving morphine had motor skills and breathing that were significantly impaired, while the rats that received endomorphin did not. The morphine rats spent more time in the compartment where they had received morphine, while the endomorphin rats did not. Only ...
Mu Opioid Receptor兔多克隆抗体(ab10275)可与小鼠, 大鼠, 豚鼠, 人样本反应并经WB, IHC, ICC, ICC/IF实验严格验证,被16篇文献引用。所有产品提供质保服务,中国75%以上现货。
Researchers found initial confirmation that a novel scaffold protein previously unassociated with the mu opioid receptor (MOR) regulates MOR-induced signaling activation. The MOR is the target of opioid drugs like morphine and is an important mechanism for pain regulation in the body. The research approach was designed to open new avenues to the treatment of chronic pain, a serious public health problem with major economic and societal costs.
The Mu Opioid Receptor Genotype May be a Marker for Those Who Drink for Alcohols Rewarding Effects, University of California, Los Angeles (UCLA) Study - read this article along with other careers information, tips and advice on BioSpace
Compare & find the top performing anti-Human Mu Opioid Receptor 1 antibody for Immunofluorescence (Paraffin-embedded Sections) (IF (p)).
|p|Endomorphins are two endogenous opioid peptides. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH|sub|2|/sub|) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH|sub|2|/sub|) are tetrapeptides with the highest known affinity and specificity for the μ opioid receptor. Endomorph
Despite the evidence from cellular and epidemiologic animal studies, clinicians should note that there are no controlled trials in humans demonstrating a direct effect of opioids in facilitating tumor progression or of opioid antagonists in attenuating tumor progression. Animal models do not uniformly translate into human disease. In addition, certain caveats apply to our work. Lewis lung carcinoma is among the most robust tumors in both growth and response to drugs. Whether our findings are applicable to other tumors or to humans is not known. In addition, the work presented in this communication deals with the effects of MOR antagonists, and the effect of chronic opioid administration has not been specifically assessed. There is considerable evidence that chronic exposure to exogenous opioids changes the response in both brain and gut.39 Whether MOR expression changes with chronic exposure in tumor cells or endothelial cells is unknown. Finally, although there may be evidence of a direct ...
Endogenous opioid-mediated reward pathways play a role in the development and maintenance of alcohol dependence. Eli Lilly and Company, a Cabernet client, therefore sought to determine whether a brain opioid-receptor antagonist (LY2196044 or LY) would reduce drinking in alcohol-dependent patients. The challenge was that pharmacotherapy of alcohol dependence shows widely divergent responses between patients, and part of this variability can be attributed to the underlying genotype. Response to the opioid-receptor antagonist naltrexone, for example, is predicted by a genetic variant of the mu-opioid receptor gene (OPRM1). Cabernet analyzed the effect of two genetic variants implicated in alcohol dependence, OPRM1 and DRD4 (dopamine-receptor subtype D4) on the efficacy of therapeutic response to LY. One OPRM1 genetic variant demonstrated an enhanced response to LY treatment when evaluated by changes in heavy drinking days (HDD), days of abstinence, or drinks per day. In addition, LY-treated ...
To elucidate the effect of an opioid on airway smooth muscle relaxant responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of the opioid mu-receptor-specific agonist DAMGO (10(-5) M) or Tyr-D-Arg-phe-Lys-NH2 (10(-5) M) did not alter the resting tension or the contractile responses to Ach but augmented the relaxation induced by isoproterenol: the concentrations of isoproterenol required to produce a half-maximal effect were decreased from 1.9 +/- 0.6 x 10(-6) to 3.1 +/- 1.0 x 10(-7) M (P , .01) by DAMGO and from 2.1 +/- 0.4 x 10(-6) M to 4.3 +/- 0.7 x 10(-7) M (P , .01), by Tyr-D-Arg-phe-Lys-NH2. This effect of DAMGO was concentration-dependent and was abolished by naloxone or Cys2, Tyr3, Orn5, Pen7-amide, a mu-receptor antagonist. DAMGO likewise caused a leftward displacement of concentration-response curves for forskolin but was without effect on those for 3-isobutyl-3-methylxanthine and 8-bromo-cAMP. Also, DAMGO did not ...
Stable recombinant cell line expressing the Opioid, Mu receptor. Human recombinant, in CHO-K1 host cell. We provide: Two vials of the recombinant cell line as frozen cells; Detailed product information including sequence, cell line properties, culture conditions, pharmacological properties of the recombinant receptor in binding and functional assays (cAMP ...
With the availability of the cDNA clones of the mu-, delta- and kappa-opioid receptors, and the elucidation of their gene structures, it is now possible to investigate opioid receptor regulation at various levels, and to identify the specific receptors involved in the pharmacological actions of the opioids ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Opioids are the gold-standard treatment for severe pain. However, potentially life-threatening side effects decrease the safety and effectiveness of these compounds. The addiction liability of these drugs has led to the current epidemic of opioid abuse in the US. Extensive research efforts have focused on trying to dissociate the analgesic properties of opioids from their undesirable side effects. Splice variants of the mu opioid receptor (MOR), which mediates opioid actions, have unique pharmacological properties and anatomic distributions that make them attractive candidates for therapeutic pain relief. In this issue of the ...
Endomorphin (EM)-1 and EM-2 are tetrapeptides located within the mammalian central nervous system and immune tissues, with high affinity and specificity for μ-opioid receptors. Most of the literature...
Symptoms of Opioid toxicity including 14 medical symptoms and signs of Opioid toxicity, alternative diagnoses, misdiagnosis, and correct diagnosis for Opioid toxicity signs or Opioid toxicity symptoms.
Get this from a library! Opioid research : methods and protocols. [Zhizhong Z Pan;] -- Opioid research has grown enormously over the last decade, and with it, the need to apply multiple techniques from a variety of disciplines. In Opioid Research: Methods and Protocols, expert ...
Mount Sinai researchers have identified unique structural, biological and chemical insights in the way different opioid drugs activate the receptors and specific signaling pathways responsible for the drugs beneficial and adverse effects, according to a study to be published in Natures Scientific Reports.
This study is the first to correlate the relative intrinsic efficacy of two MOPr signaling outputs for such a wide range of opioid ligands. It shows that, for these MOPr agonists, there is a strong positive correlation between the operational efficacies for G protein activation and arrestin-3 recruitment. Previous studies have provided very useful measures of relative intrinsic activity for MOPr agonists (Traynor and Nahorski, 1995; Yu et al., 1997; Kovoor et al., 1998; Zaki et al., 2000; Clark et al., 2006; Saidak et al., 2006), however this parameter is not able to differentiate full agonists in terms of efficacy and can be highly dependent upon receptor expression levels, so for these reasons, operational efficacy is a more useful measure. The operational model of agonism provides a measure of efficacy, termed operational efficacy, or τ (Black and Leff, 1983). Because τ is equal to RT/Ke (where RT is the receptor concentration in the tissue and Ke is the concentration of agonist-receptor ...
The first look at how the opioid epidemic is affecting children shows that just as with adults, rates of hospitalizations for opioid poisonings are climbing among young people
The opioid crisis has claimed 64,000 lives in 2016 which is more than the entire death toll of the Vietnam War. Following current trends, there appears to be no end in sight for this emergency. A related offshoot of the opioid epidemic is a largely overlooked and gravely underfunded public healt ...
The synthesis and magnetic characterisation of a series of bis-mu-alkoxide bridged MnIII dinuclear complexes of general formula [MnIII2(mu-OR)2(biphen)2(ROH)x(L)y] (where R=Me, Et; H2biphen=2,2-biphenol and L=terminally ...
/PRNewswire/ -- ZeOmega, the nations leading provider of technology-enabled population health solutions, today announced the release of Jiva Opioid AI, an...
Its being called grey death -- a new and dangerous opioid combo that underscores the ever-changing nature of the U.S. addictions epidemic.
The opioid epidemic is a problem in need of solutions but the problems size puts it outside the scope of any one group. Instead, it requires collaboration.
Opioid je hemijsko jedinjenje koje se vezuje za opioidne receptore, koji se nalaze prvenstveno u centralnom nervnom sistemu i gastrointestinalnom traktu. Ovi receptori u tim organima posreduju blagotvorne kao i sporedne efekte opioida.[1][2] Analgetski efekti opioida dolaze os umanjenog percepcije bola, umanjene reakcije na bol kao i povećane tolerancije bola. Nepoželjni efekti opioida su sedacija, respiratorna depresija, i konstipacija. Opioidi mogu da uzrokuju umanjenje kašlja. Fizička zavisnost može da se razvije tokom njihove administracije, koja dovodi do sindroma povlačenja kod naglog prekida upotrebe. Opioidi mogu da proizvedu osećanje euforije. ...
Across the country, the opioid crisis has led communities to see how they can curb the number of deaths connected with these types of drugs.
A Reaganesque ad campaign aimed at telling kids that drugs are bad is the latest gigantic waste of time and money in attempting to solve the opioid crisis.
Scores of sober-living houses have quietly opened throughout Maine in recent years. In them, hundreds of people battling addiction pay monthly rent, mostly out of pocket, to live and recover alongside their peers.
MS Contin is an opioid agonist that is used to manage pain severe enough to require daily, around-the-clock, long-term treatment.
Weve been fostering specifically because of the need that weve seen and the knowledge that children are in the system who dont really have any other choice.
I woke up at the ungodly hour of 7:45 this morning and wished I hadnt. It took me several long minutes of stretching and yawning and stretching and mor...
Mu and kappa opioid receptors often show antagonism in the regulation of physiological responses and behavior, including aggressive behavior. We report here our studies of the effects of acute administration of the selective mu opioid receptor antagonist CTAP (1 and 2 mg/kg, s.c.) and the selective kappa opioid receptor antagonist nor-BNI (0.5 mg/kg, s.c.) on manifestations of aggressive behavior in male C57BL/6 J mice with short (three days) and long (20 days) experience of victory in intermale confrontations. Animals with short experience of aggression were insensitive to blockade of both mu and kappa receptors. In males with long experience of aggression, administration of CTAP led to dose-dependent increases in the latent period of attacks but had no effect on attack duration. Administration of nor-BNI had no effect on the behavior of males with prolonged experience of aggression in antagonistic confrontations. Possible changes in the sensitivity of opioid receptors in male C57BL/6 J mice ...
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TY - JOUR. T1 - Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors. AU - Gulya, K.. AU - Pelton, John T.. AU - Hruby, Victor J.. AU - Yamamura, Henry I.. PY - 1986/6/16. Y1 - 1986/6/16. N2 - A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14- somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the syntheis of our most potent and selective mu opioid receptor compound DPheCysTyrDTrpOrnThrPenThrNH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 ± 0.1) and exceptional ...
There is considerable controversy over whether μ-opioid receptor (MOPr) desensitization is homologous or heterologous and over the mechanisms underlying such desensitization. In different cell types MOPr desensitization has been reported to involve receptor phosphorylation by various kinases, including G-protein-coupled receptor kinases (GRKs), second messenger and other kinases as well as perturbation of the MOPr effector pathway by GRK sequestration of G protein βγ subunits or ion channel modulation. Here we report that in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8 weeks old) rapid MOPr desensitization induced by the high-efficacy opioid peptides methionine enkephalin and DAMGO was homologous and not heterologous to α2-adrenoceptors and somatostatin SST2 receptors. Given that these receptors all couple through G proteins to the same set of G-protein inwardly rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr desensitization ...