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14-September-2008 18:02:44 - mu Opioid receptor Opioid receptor, mu 1 Identifiers Symbols OPRM1; MOR1; KIAA0403; OPRM External IDs OMIM: 600018 MGI: 97441 HomoloGene: 37368 Gene ontology Molecular function: rhodopsin-like receptor activity receptor activity mu-opioid receptor activity Cellular component: endoplasmic reticulum Golgi apparatus plasma membrane integral to plasma membrane membrane integral to membrane Biological process: signal transduction G-protein coupled receptor protein signaling pathway G-protein signaling, coupled to cyclic nucleotide second messenger sensory perception behavior negative regulation of cell proliferation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 4988 18390 Ensembl ENSG00000112038 ENSMUSG00000000766 Uniprot P35372 Q8CH75 Refseq NM_000914 mRNA NP_000905 protein XM_001052051 mRNA XP_001052051 protein Location Chr 6: 154.4 - 154.61 Mb Chr 10: 3.33 - 3.59 Mb Pubmed search 1 2 Active and inactive μ-opioid receptors. Active and inactive μ-opioid receptors.1 The μ opioid receptors MOR are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. The prototypical μ receptor agonist is the opium alkaloid morphine; μ mu refers to morphine. Certain other opiates, notably codeine and heroin are prodrugs that are metabolized into morphine. Contents 1 Types 2 Location 3 Activation 4 Tolerance and overdoses 5 References 6 External links Types There are three known variants of the μ opioid receptor.2 More is known about the μ1 opioid receptor than is known about the other types, but some information does exist. TRIMU 5 is a selective agonist of the μ2 receptor.3 In 2003, a μ3 variant was described,4 which was responsive to opiate alkaloids but not opioid peptides.5 Location They can exist either presynaptically or postsynaptically depending upon cell types. The μ-receptors exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord specifically the substantia gelatinosa of Rolando. Other areas where μ-receptors have been located include the external plexiform layer of the olfactory bulb, the nucleus accumbens, in several layers of the cerebral cortex and in some of the nuclei of the amygdala, as well as the nucleus of the solitary tract. μ receptors are also found in the intestinal tract. This causes constipation, a major side effect of μ agonists, due to inhibition of peristaltic action. Activation MOR can mediate acute changes in neuronal excitability via disinhibition of presynaptic release of GABA see works from Charles Chavkin and Roger Nicoll. Activation of the MOR leads to different effects on dendritic spines depending upon the agonist, and may be an example of functional selectivity at the μ receptor see works from Dezhi Liao and Horace Loh. The physiological and pathological roles of these two distinct mechanisms remain to be clarified. Perhaps, both might be involved in opioid addiction and opioid-induced deficits in cognition. Activation of the μ receptor by an agonist such as morphine causes analgesia, sedation, slightly reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis constricted pupils and decreased bowel motility often leading to constipation. Some of these side effects, such as sedation, euphoria and decreased respiration, tend to lessen with continued use as tolerance develops. Analgesia, miosis and reduced bowel motility tend to persist; little tolerance develops to these effects. Tolerance and overdoses Opioid overdoses kill through apnea and fatal hypoxia, often aggravated by simultaneous use of alcohol, benzodiazepines or barbiturates. However, substantial tolerance to respiratory depression develops quickly and tolerant individuals can easily withstand large doses fatal to opioid naïve individuals an example of Mithridatism. Less commonly, massive overdoses have been known to cause circulatory collapse. Tolerance to respiratory depression is lost just as quickly during withdrawal. Many, if not most fatal overdoses occur in addicts who take their usual doses after being in withdrawal long enough to lose their tolerance to respiratory depression. Opioid overdoses can be rapidly reversed with any of several opioid antagonists: naloxone, or naltrexone, differing primarily in their duration of action and potency. While commonly referred to as antagonists, and when used to treat an overdose they do appear to function as such, naloxone naltrexone are inverse agonists. References ^ Zhorov BS, Ananthanarayanan VS. Homology models of μ-opioid receptor with organic and inorganic cations at conserved aspartates in the second and third transmembrane domains. Arch Biochem Biophys. 37:31-49, 2000. ^ Dortch-Carnes J, Russell K 2007. Morphine-stimulated nitric oxide release in rabbit aqueous humor. Exp. Eye Res. 84 1: 185-90. doi:10.1016/j.exer.2006.09.014. PMID 17094965. ^ Eisenberg RM 1994. TRIMU-5, a μ2-opioid receptor agonist, stimulates the hypothalamo-pituitary-adrenal axis. Pharmacol. Biochem. Behav. 47 4: 943-6. PMID 8029266. ^ Cadet P, Mantione KJ, Stefano GB 2003. Molecular identification and functional expression of μ3, a novel alternatively spliced variant of the human μ opiate receptor gene. J. Immunol. 170 10: 5118-23. PMID 12734358. ^ Stefano GB 2004. Endogenous morphine: a role in wellness medicine. Med. Sci. Monit. 10 6: ED5. PMID 15173675. External links IUPHAR GPCR Database - μ opioid receptor MeSH mu+Opioid+Receptor v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened v d e Neuropeptide receptors Hypothalamic hormone receptors CRH - FSH - LHRH - TRH - Somatostatin Pituitary hormone receptors Vasopressin 1A, 1B, 2 - Oxytocin - LHCG - Type I cytokine receptor GH, Prolactin - TSH Other hormone receptors Atrial natriuretic factor - Calcitonin - Cholecystokinin A, B - VIP Opioid receptors Delta - Kappa - Mu - Sigma 1, 2 - Nociceptin Other neuropeptide receptors Angiotensin - Bradykinin B1, B2 / Tachykinin TACR1 - Calcitonin gene-related peptide - Galanin - GPCR neuropeptide B/W, FF, S, Y - Neurotensin Retrieved from http://en..org/wiki/Mu_Opioid_receptor Categories: Genes on chromosome 6 | Human proteins | Cell signaling | Signal transduction | Opioid receptorHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Français This page was last modified on 7 September 2008, at 02:13
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