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)

Remifentanil is a new selective mu opioid receptor agonist of higher potency than alfentanil, with pharmacological effects that essentially parallel those of alfentanil and other opioids in this class. Unlike other opioids, remifentanil is rapidly hydrolysed by nonspecific plasma and tissue esterases: this imparts brevity of action, precise and rapidly titratable effects (due to rapid onset and offset), non-cumulative opioid effects and rapid recovery after cessation of administration. The onset of action of remifentanil is similar to that of alfentanil, although its offset is considerably more rapid and independent of the duration of infusion. Remifentanil also has a sparing effect on hypnotics and sedatives. Its brevity of action ensures not only a rapid resolution of adverse effects but also a rapid offset of analgesic effect. Therefore, appropriate postoperative analgesia, when necessary, should be established before discontinuation of remifentanil infusion. The unique pharmacokinetic profile of remifentanil facilitates 'real time' management of intraoperative stress, as well as provision of optimal intraoperative analgesia without compromising recovery for a variety of surgical procedures.
Drugs 1996 Sep
PMID:Remifentanil. 887 31

The rapid metabolism of heroin to 6-acetylmorphine and its slower conversion to morphine has led many to believe that heroin and morphine act through the same receptors and that the differences between them are due to their pharmacokinetics. We now present evidence strongly implying that heroin and two potent mu drugs, fentanyl and etonitazine, act through a unique receptor mechanism similar to morphine-6 beta-glucuronide which is readily distinguished from morphine. Heroin, 6-acetylmorphine and morphine-6 beta-glucuronide show no analgesic cross tolerance to morphine in a daily administration paradigm, implying distinct receptors. Strains also reveal analgesic differences among the drugs. CXBK mice, which are insensitive to morphine, retain their analgesic sensitivity to heroin, 6-acetylmorphine, morphine-6 beta-glucuronide, fentanyl and etonitazine. Antisense mapping of the mu opioid receptor MOR-1 reveals that oligodeoxynucleotide probes against exon 2, which are inactive against morphine analgesia, block morphine-6 beta-glucuronide, heroin, fentanyl and etonitazine analgesia. Finally, an antisense probe targeting Gi alpha 1 blocks both heroin and morphine-6 beta-glucuronide, but not morphine, analgesia. These results indicate that heroin, 6-acetylmorphine, fentanyl and etonitazine all can produce analgesia through a novel mu analgesic system which is similar to that activated by morphine-6 beta-glucuronide.
Neurosci Lett 1996 Sep 20
PMID:Novel receptor mechanisms for heroin and morphine-6 beta-glucuronide analgesia. 889 77

Using a combination of radioactive and non-radioactive in situ hybridization, the mu opioid receptor mRNA was localized in enkephalin as well as dynorphin neurones of the rat striatum. The proportion of enkephalin neurones showing co-localized mu opioid receptor mRNA was dependent on the rostrocaudal level (17-39% in rostral/intermediate levels vs 0.4-5% caudally) but did not differ between striatal subregions. For dynorphin neurones the reverse was true, with consistently higher levels of co-localization in the caudate-putamen (56-77%) than the nucleus accumbens (15-43%), but no differences along the rostrocaudal axis. Furthermore, the degree of enkephalin/mu co-localization was significantly lower than that of dynorphin/mu. These results suggest a fine-grained topological differentiation of mu receptor modulation of striatal opioid systems.
Neuroreport 1996 Sep 02
PMID:Co-localization of mu opioid receptor is greater with dynorphin than enkephalin in rat striatum. 893 Sep 71

The mu opioid receptor mediates ingestive behavior: mu-selective agonists stimulate food intake and antagonists reduce intake in many ingestive situations. Antisense oligodeoxynucleotides directed against each of the four exons of the MOR-1 clone were equally effective in reducing spontaneous food intake and body weight in rats. However, antisense probes directed against only exon 1 or 4 of the MOR-1 clone reduced mu-mediated analgesia. The present study examined whether central administration of antisense probes directed against each of the four exons of the MOR-1 clone or a missense control altered hyperphagia elicited by the mu agonist DAMGO across a range of doses. Antisense probes directed against only exon 1 or 4 blocked hyperphagia at agonist doses of 0.5 and 1.0 microg; this pattern was identical to that observed for mu-mediated analgesia. A missense control failed to exert significant effects, which suggests specificity of antisense actions. The effective antisense probes failed to reduce hyperphagia at a higher (5 microg) agonist dose, a result consistent with limitations in down-regulation of receptor proteins by antisense. The mu antagonist beta-funaltrexamine produced a similar pattern of effects on mu-mediated hyperphagia. The selective actions of antisense probes directed against different exons of the MOR-1 clone in reducing hyperphagia induced by DAMGO suggest that multiple splice variants of the MOR-1 clone exist and raise the possibility of further opioid receptor subclassifications.
J Pharmacol Exp Ther 1997 Sep
PMID:Antisense mapping of the MOR-1 opioid receptor clone: modulation of hyperphagia induced by DAMGO. 931 53

The mu opioid receptor is concentrated in laminae I and II (LI and LII, respectively) of the normal rat dorsal horn. Fourteen days after transection of the L4-L6 segmental peripheral nerves, image analysis demonstrates a 49, 34 and 17% decrease in mu opioid staining density in the medial, middle and lateral thirds of the superficial dorsal horn, respectively, when comparing the operated to the unoperated side. Intralaminar analysis demonstrates that the greatest change in density occurs in LI and LII outer, compared to LII inner. By 31 days post-surgery, staining has returned to normal with side to side differences no longer present. These results imply that mu opioid ligands such as morphine might be less effective in ameliorating pain 2 weeks after a peripheral nerve lesion than they are in the normal condition, but that this effectiveness should return as the receptors are restored to their normal levels. Thus, the time following a lesion may be an important variable in assessing the effectiveness of mu opioid ligands in alleviating neuropathic pain. Furthermore, this study shows that the organization of opioid receptors in the superficial dorsal horn is malleable and could lead to changes in drug efficacy.
Neurosci Lett 1997 Sep 19
PMID:The reorganization of mu opioid receptors in the rat dorsal horn following peripheral axotomy. 935 Aug 45

Tramadol is an atypical centrally acting analgesic agent with relatively weak opioid receptor affinity in comparison with its antinociceptive efficacy. Evidence suggests that block of monoamine uptake may contribute to its analgesic actions. Therefore, we have examined the actions of (+/-)-tramadol, (+)-tramadol, (-)-tramadol and O-desmethyltramadol (M1 metabolite) on electrically evoked 5-HT efflux and uptake in the dorsal raphe nucleus (DRN) brain slice, measured by fast cyclic voltammetry. Racemic tramadol and its (+)-enantiomer (both 5 mumol litre-1) significantly blocked DRN 5-HT uptake (both P < 0.05) and increased stimulated 5-HT efflux (P < 0.01 (+/-)-tramadol; P < 0.05 (+)-tramadol). The (-)-enantiomer and metabolite, O-desmethyltramadol, were inactive at the concentration tested (5 mumol litre-1). For both (+/-)-tramadol and the (+)-enantiomer, the action on 5-HT efflux preceded an effect on 5-HT uptake, suggesting that uptake block was not the cause of the increased 5-HT efflux and that tramadol might therefore have a direct 5-HT releasing action. This activity, at clinically relevant concentrations, may help to explain the antinociceptive efficacy of tramadol despite weak mu opioid receptor affinity and adds to evidence that tramadol exerts actions on central monoaminergic systems that may contribute to its analgesic effect.
Br J Anaesth 1997 Sep
PMID:Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. 938 55

The role of beta-arrestin 1 (beta-arr1) in regulation of responsiveness of kappa, delta, and mu opioid receptors has been investigated in human embryonic kidney 293 cells cotransfected with opioid receptor and beta-arr1. Expression of human beta-arr1 attenuated kappa and delta opioid receptor subtype-mediated inhibition of cAMP production and resulted in a 100-fold increase of EC50 values for kappa-agonist U69593 and delta-agonist [D-Pen2, D-Pen5]enkephalin and 30-40% reduction of their maximal responses. In contrast, coexpression of beta-arr1 with mu opioid receptor did not affect the concentration-effect relationship of mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin. In parallel, kappa and delta receptor-mediated G protein activation was also remarkably attenuated by overexpression of beta-arr1, while the mu-agonist-stimulated response remained intact. These results indicate that beta-arr1 interferes receptor/G protein coupling and differentially regulates the responsiveness of opioid receptors. Truncation of kappa and delta opioid receptors at carboxyl termini abolished inhibition of beta-arr1 on the responsiveness of both receptors. Furthermore, mu opioid receptor became sensitive to beta-arr1 regulation following replacement of its carboxyl terminus with the corresponding portion of the delta receptor. Removal of potential phosphorylation sites on the carboxyl terminus of kappa opioid receptor led to reduced effect of beta-arr1 on the receptor-mediated response. These results suggest that receptor carboxyl terminus and its phosphorylation play an important role in the interaction of beta-arr1 and opioid receptors.
J Biol Chem 1998 Sep 18
PMID:Selective interference of beta-arrestin 1 with kappa and delta but not mu opioid receptor/G protein coupling. 973 19

Mu and delta opioid receptors have been demonstrated to mediate supraspinal opioid antinociception. Whereas the recombinant inbred CXBK mouse is notably deficient in mu opioid receptor antinociception, binding density, and mRNA (MOR-1) levels, little is known about delta opioid receptor processes in this strain. The present study thus compared CXBK mice and their BALB/c strain progenitors with respect to delta opioid antinociception, whole-brain receptor binding levels, and mRNA (DOR-1) levels. Following intracerebroventricular injections of the selective delta1 and delta2 opioids DPDPE and [d-Ala2]deltorphin II, respectively, CXBK mice displayed relatively lower antinociception on the tail-flick test, resulting in significantly increased ED50 values for both agonists in this strain. Decreased whole-brain specific binding of [3H][d-Ala2]deltorphin II, but not [3H]DPDPE, was also observed in CXBK mice. Solution hybridization with a probe for the DOR-1 revealed increased transcript levels in the caudate-putamen, frontal cortex, and spinal cord of this strain. The present data demonstrate a deficiency in delta1 and delta2 opioid antinociception in CXBK mice concomitant with reductions in whole-brain delta2 receptor binding and regional increases in DOR-1. Whether these observations are causally related remains to be clarified.
Brain Res 1998 Sep 14
PMID:Differences in delta opioid receptor antinociception, binding, and mRNA levels between BALB/c and CXBK mice. 973 48

Opioidergic neurotransmission and, specifically, the mu opioid receptor have been implicated in the reinforcing effects of a variety of drugs of abuse. Consequently, the present study examined the association of a polymorphic (CA)n repeat at the OPRM1 locus (the gene coding for the mu opioid receptor) to alcohol or drug dependence in 320 Caucasian and 108 African-American substance-dependent or control subjects. Among Caucasians, suggestion of a modest association, which could be interpreted as statistically significant (p = 0.03), was observed between OPRM1 alleles and substance (alcohol, cocaine, or opioid) dependence. Analysis by specific substance showed only a trend level association to alcohol dependence. Comparisons among African Americans yielded no evidence for association. Further studies of the association between alleles of the OPRM1 gene and substance dependence appear warranted, particularly if they use a family-based approach to control for population stratification. Phenotypes other than a broad diagnostic categorization, such as opioid antagonist effects on drinking behavior in alcoholics, may provide more consistent evidence of a role for OPRM1 in behavioral variability.
Alcohol Clin Exp Res 1998 Sep
PMID:Association of alcohol or other drug dependence with alleles of the mu opioid receptor gene (OPRM1). 975 53

We determined allele frequencies for polymorphisms at several loci of interest in neuropsychiatry-tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), ciliary neurotrophic factor (CNTF), and the mu opioid receptor (OPRM1)-in samples of individuals from populations in several different parts of the world. Associations with psychiatric illness have been proposed for specific polymorphisms at TPH (suicide-related behaviors and impulsivity), DRD3 (schizophrenia and bipolar affective disorder), SLC6A3 (susceptibility to cocaine-induced paranoia and attention-deficit disorder), CNTF (psychosis), and OPRM1 (substance dependence). APOE alleles are related to risk of Alzheimer disease. We found significant allele frequency variation among populations at all six loci. These results will provide a global framework of normal variation at these loci that might have functional significance or otherwise be related to susceptibility to various disorders or behavioral phenomena. Knowledge of this variation can be important for study design and data interpretation when individuals from various population groups are research subjects and may eventually help lead to a better understanding of behavioral adaptation.
Genomics 1998 Sep 15
PMID:Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). 979 Jul 47


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