Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:025300 (mu opioid receptor)
 1,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid peptides are the most effective drugs in controlling pain; their action is elicited by binding to specific membrane receptors. The gastrointestinal tract represents, after the nervous system, the site in which the opioid receptors are expressed at high levels. The opioid agonist morphine has a significant inhibitory effect on intestinal motility, this action is blocked by naloxone an opioid antagonist mainly active at mu and kappa receptors. In this study the presence of mu opioid receptor on rabbit jejunum was investigated by western blot. The effects of beta-endorphin, the endogenous opioid peptide with the highest affinity to the mu opioid receptor and those of naloxone on spontaneous rabbit jejunum contractions were evaluated. Beta-endorphin (10(-6) M) showed a relaxant effect on jejunum contractility while naloxone showed a dual effect inducing an increase of spontaneous contractility at low concentrations (10(-6) M, 10(-7) M, 10(-8) M) and a decrease when high concentrations (10(-3) M, 10(-4) M, 10(-5) M) were utilized. The obtained results demonstrate that mu opioid receptor is expressed in rabbit jejunum and suggest that this receptor may be involved in mediating the effects of both opioid agonist and antagonist on jejunum contractions.
J Physiol Pharmacol 2006 Sep
PMID:Opioid agonist/antagonist effect of naloxone in modulating rabbit jejunum contractility in vitro. 1703 96

The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon gamma, tumor necrosis factor alpha, and interleukin-1beta, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), on cytokine induced iNOS expression in human astroglia. beta-FNA dose-dependently inhibited iNOS expression. beta-FNA transcriptionally (or pre-transcriptionally) inhibited cytokine-induced iNOS activation as indicated by a significant decrease in NOS2 messenger RNA expression. Further characterization of the novel, anti-inflammatory actions of beta-FNA may provide insights for pharmacologic strategies to treat or prevent brain pathologies associated with neuroinflammation.
J Neuroimmune Pharmacol 2008 Sep
PMID:Beta-funaltrexamine inhibits inducible nitric-oxide synthase expression in human astroglial cells. 1827 57

Recent evidence indicates that agonist ligands of G protein coupled receptors (GPCR) can activate different signaling systems. Such "agonist-directed" signaling also occurs with opioid receptors. Previous work from our laboratory showed that chronic morphine, but not DAMGO, up-regulates the expression of Galpha12 and that both morphine and DAMGO decreased Galphai3 expression in CHO cells expressing the cloned human mu opioid receptor. In this study, we tested the hypothesis that chronic opioid regulation of G protein expression is agonist-directed. Following a 20h treatment of CHO cells expressing the cloned human mu (hMOR-CHO), delta (hDOR-CHO) or kappa (hKOR-CHO) opioid receptors with various opioid agonists, we determined the expression level of Galpha12 and Galphai3 by Western blots. Among five mu agonists (morphine, etorphine, DADLE, DAMGO, herkinorin) tested with hMOR-CHO cells, only chronic morphine and etorphine up-regulated Galpha12 expression. All five mu agonists decreased Galphai3 expression. Among six delta agonists (SNC80, DPDPE, deltorphin-1, morphine, DADLE, etorphine) tested with hDOR-CHO cells, all six agonists down-regulated Galphai3 expression or moderately up-regulated Galpha12 expression. Among five kappa agonists, ((-)-ethylketocyclazocine, salvinorin A, U69,593, etorphine, (-)-U50,488) tested with hKOR-CHO cells, only chronic (-)-U50,488 and (-)-EKC up-regulated Galpha12 expression. All kappa agonists decreased Galphai3 expression. These data demonstrate that chronic opioid agonist regulation of G protein expression depends not only on the agonist tested, but also on the type of opioid receptor expressed in a common cellular host, providing additional evidence for agonist-directed signaling.
Brain Res Bull 2008 Sep 05
PMID:Differential effects of opioid agonists on G protein expression in CHO cells expressing cloned human opioid receptors. 1863 45

Genetic variation may influence initial sensitivity to nicotine (i.e. during early tobacco exposure), perhaps helping to explain differential vulnerability to nicotine dependence. This study explored associations of functional candidate gene polymorphisms with initial sensitivity to nicotine in 101 young adult nonsmokers of European ancestry. Nicotine (0, 5, 10 microg/kg) was administered through nasal spray followed by mood, nicotine reward (e.g. 'liking') and perception (e.g. 'feel effects') measures, physiological responses, sensory processing (prepulse inhibition of startle), and performance tasks. Nicotine reinforcement was assessed in a separate session using a nicotine versus placebo spray choice procedure. For the dopamine D4 receptor [DRD4 variable number of tandem repeats (VNTR)], presence of the 7-repeat allele was associated with greater aversive responses to nicotine (decreases in 'vigor', positive affect, and rapid information processing; increased cortisol) and reduced nicotine choice. Individuals with at least one DRD4 7-repeat allele also reported increased 'feel effects' and greater startle response, but in men only. Other genetic associations were also observed in men but not women, such as greater 'feel effects' and anger, and reduced fatigue, in the dopamine D2 receptor (DRD2 C957T single nucleotide polymorphism) TT versus CT or CC genotypes. Very few or no significant associations were seen for the DRD2/ANKK1 TaqIA polymorphism, the serotonin transporter promoter VNTR or 5HTTLPR (SLC6A4), the dopamine transporter 3' VNTR (SLC6A3), and the mu opioid receptor A118G single nucleotide polymorphism (mu opioid receptor polymorphism 1). Although these results are preliminary, this study is the first to suggest that genetic polymorphisms related to function in the dopamine D4, and perhaps D2, receptor may modulate initial sensitivity to nicotine before the onset of dependence and may do so differentially between men and women.
Behav Pharmacol 2008 Sep
PMID:Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers. 1869 Jan 17

Analgesic tolerance to morphine can develop from long-term use of this drug for the treatment of pain. Many reports have shown that stimulation of the kappa opioid receptor (KOR) suppresses development of analgesic tolerance to morphine. Here, we studied the KOR-mediated inhibition of morphine tolerance during repeated morphine treatment, with a focus on desensitization of the receptor. The development of analgesic tolerance to morphine during repeated morphine administration (10 mg kg(-1) s.c.) was completely suppressed by U-50488H (2 mg kg(-1) i.p.), a KOR agonist. The decrease in [35S] GTPgammaS binding activity stimulated by the mu opioid receptor (MOR) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) was also significantly inhibited by U-50488H. These results indicate that stimulation of KOR caused by repeated morphine treatment either inhibits MOR desensitization or accelerates recycling of MOR on the cell surface, thereby suppressing morphine tolerance. Furthermore, we found that activity of protein kinase C (PKC) was significantly decreased in mice treated with both U-50488H and morphine. These results suggest that the mechanisms underlying KOR-mediated inhibition of analgesic tolerance to morphine may be partly due to suppression of PKC activation and prevention of receptor desensitization.
J Pharm Pharmacol 2008 Sep
PMID:Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment. 1871 22

The slow aggregation assay is generally used to study the functionality of cell-cell adhesion complexes. Single cells are seeded on a semisolid agar substrate in a 96-well plate and the cells spontaneously aggregate. We used HEK FLAG-MOP cells that stably overexpress the mu opioid receptor and the mu-opioid-receptor-selective agonists DAMGO and morphine to study whether other factors than functionality of cell-cell adhesions complexes can contribute to changes in the pattern of slow aggregation on agar. HEK FLAG-MOP cells formed small compact aggregates. In the presence of DAMGO and morphine, larger and fewer aggregates were formed in comparison to the vehicle control. These aggregates were localized in the center of the agar surface, whereas in the vehicle control they were dispersed over the substrate. However, in suspension culture on a Gyrotory shaker, no stimulation of aggregation was observed by DAMGO and morphine, showing that opioids do not affect affinity. A dissociation experiment revealed that HEK FLAG-MOP aggregates formed in the absence or presence of opioids are resistant to de-adhesion. We demonstrated that the larger aggregates are neither the result of cell growth stimulation by DAMGO and morphine. Since manipulations of the substrate such as increasing the agar concentration or mixing agar with agarose induced the same changes in the pattern of slow aggregation as treatment with opioids, we suggest that cell-substrate adhesion may be involved in opioid-stimulated aggregation.
In Vitro Cell Dev Biol Anim 2009 Sep
PMID:Cell aggregation on agar as an indicator for cell-matrix adhesion: effects of opioids. 1924 23

The endogenous hippocampal opioid systems are implicated in learning associated with drug use. Recently, we showed that ovarian hormones regulate enkephalin levels in the mossy fiber pathway. This pathway overlaps with parvalbumin (PARV)-basket interneurons that contain the enkephalin-activated mu opioid receptors (MORs) and are important for controlling the "temporal timing" of granule cells. Here, we evaluated the influence of ovarian steroids on the trafficking of MORs in PARV interneurons. Two groups of female rats were analyzed: cycling rats in proestrus (relatively high estrogens) or diestrus; and ovariectomized rats euthanized 6, 24 or 72 h after estradiol benzoate (10 microg, s.c.) administration. Dorsal hippocampal sections were dually immunolabeled for MOR and PARV and examined by light and electron microscopy. As in males, in females MOR-immunoreactivity (-ir) was in numerous PARV-labeled perikarya, dendrites and terminals in the dentate hilar region. Variation in ovarian steroid levels altered the subcellular distribution of MORs in PARV-labeled dendrites but not terminals. In normal cycling rats, MOR-gold particles on the plasma membrane of small PARV-labeled dendrites (area <1 microm2) had higher density in proestrus rats than in diestrus rats. Likewise, in ovariectomized rats MORs showed higher density on the plasma membrane of small PARV-labeled dendrites 72 h after estradiol exposure. The number of PARV-labeled cells was not affected by estrous cycle phase or estrogen levels. These results demonstrate that estrogen levels positively regulate the availability of MORs on GABAergic interneurons in the dentate gyrus, suggesting cooperative interaction between opioids and estrogens in modulating principal cell excitability.
Exp Neurol 2009 Sep
PMID:Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneurons. 1950 58

The molecular docking of a series of endomorphin analog with the mu opioid receptor was performed. The successive molecular dynamics of several proposed ligand-receptor complexes inserted into the phospholipid bilayer were carried out to optimize the complex and explore the conformational changes. Meaningful differences of their binding modes were detected and the involvement of some essential residues in ligand binding was also identified. Our proposed ligand-receptor model is in good agreement with previous site-directed mutagenesis experiments.
Bioorg Med Chem Lett 2009 Sep 15
PMID:Molecular modeling studies to predict the possible binding modes of endomorphin analogs in mu opioid receptor. 1967 74

The functional characterization of the mu opioid receptor from the zebrafish (zfMOR) is reported here. After transfection in HEK-293 cell line, using both peptidergic and nonpeptidergic opioid ligands in the competition and saturation-binding experiments, in addition to the functional assays of (35)S-GTPgammaS-binding assays and intracellular 3'-5'-cyclic adenosine monophosphate (cAMP) level determinations, we demonstrate that zfMOR exhibits a pharmacological profile similar to that of the mammalian MOR. Besides, the internalization process of zfMOR after opiate agonist treatment (morphine, DAMGO, etorphine) resembles the pattern observed for its mammalian counterpart. These similarities suggest that the zebrafish is a good model for the study of the opioid effects in development.
Zebrafish 2009 Sep
PMID:Mu opioid receptor from the zebrafish exhibits functional characteristics as those of mammalian mu opioid receptor. 1976 79

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and mu opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at >or=2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the chi2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using chi2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP.
Mol Pain 2009 Sep 23
PMID:Do genetic predictors of pain sensitivity associate with persistent widespread pain? 1977 52


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