WordNet

plaster with mud
water soaked soil; soft wet earth (同)clay
slanderous remarks or charges
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
the 12th letter of the Greek alphabet

PrepTutorEJDIC

『泥』;ぬかるみ
=sense organ / 受信装置
ミュー(ギリシア語アルファベットの第12字М,μ;英語のM,mに相当)
museum / music

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/19 01:09:19」(JST)

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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. They are also referred to as μ opioid peptide (MOP) receptors. The prototypical μ receptor agonist is morphine, the primary psychoactive alkaloid in opium.

Types

Three variants of the μ opioid receptor are well-characterized, though reverse-transcriptase PCR has identified up to 10 total splice variants in humans.^[2]^[3]

μ₁	More is known about the μ₁ opioid receptor than the other variants.
μ₂	TRIMU 5 is a selective agonist of the μ₂ receptor.^[4]
μ₃	The μ₃ variant was first described in 2003.^[5] It is responsive to opiate alkaloids but not opioid peptides.^[6]

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. Activation of these receptors inhibits peristaltic action which causes constipation, a major side effect of μ agonists.^[7]

Activation

MOR can mediate acute changes in neuronal excitability via "disinhibition" of presynaptic release of GABA. 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.^[8] 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 effects, such as analgesia, sedation, euphoria and decreased respiration, tend to lessen with continued use as tolerance develops. Miosis and reduced bowel motility tend to persist; little tolerance develops to these effects.

The canonical MOR1 isoform is responsible for morphine-induced analgesia whereas the alternatively spliced MOR1D isoform (through heterodimerization with the gastrin-releasing peptide receptor) is required for morphine-induced itching.^[9]

Deactivation

As with other G protein-coupled receptors, signalling by the mu opioid receptor is terminated through several different mechanisms, which are upregulated with chronic use, leading to rapid tachyphylaxis.^[10] The most important regulatory proteins for the mu opioid receptor are the β-arrestins Arrestin beta 1 and Arrestin beta 2,^[11]^[12]^[13] and the RGS proteins RGS4, RGS9-2, RGS14 and RGSZ2.^[14]^[15]

Long-term or high dose use of opioids may also lead to additional mechanisms of tolerance becoming involved. This includes downregulation of mu opioid receptor gene expression, so the number of receptors presented on the cell surface is actually reduced, as opposed to the more short-term desensitisation induced by β-arrestins or RGS proteins.^[16]^[17]^[18] Another long-term adaptation to opioid use can be upregulation of glutamate and other pathways in the brain which can exert an opioid-opposing effect and so reduce the effects of opioid drugs by altering downstream pathways, regardless of mu opioid receptor activation.^[19]^[20]

Tolerance and overdoses

Opioid overdoses kill through apnea and fatal hypoxia, often caused by combination with ethanol, benzodiazepines or barbiturates. Substantial tolerance to respiratory depression develops quickly, and tolerant individuals can withstand larger doses. However tolerance to respiratory depression is lost just as quickly during withdrawal. Many^{[citation needed]} overdoses occur in people who misuse their medication after being in withdrawal long enough to lose the tolerance to respiratory depression. Less commonly, massive overdoses have been known to cause circulatory collapse.

Opioid overdoses can be rapidly reversed through the use of opioid antagonists, naloxone being the most widely used example.

References

^ Zhorov BS, Ananthanarayanan VS (March 2000). "Homology models of mu-opioid receptor with organic and inorganic cations at conserved aspartates in the second and third transmembrane domains". Arch. Biochem. Biophys. 375 (1): 31–49. doi:10.1006/abbi.1999.1529. PMID 10683246.
^ 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. PMC 1766947. PMID 17094965.
^ Pan L, Xu J, Yu R, Xu MM, Pan YX, Pasternak GW (2005). "Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm". Neuroscience. 133 (1): 209–20. doi:10.1016/j.neuroscience.2004.12.033. PMID 15893644.
^ Eisenberg RM (1994). "TRIMU-5, a μ₂-opioid receptor agonist, stimulates the hypothalamo-pituitary-adrenal axis". Pharmacol. Biochem. Behav. 47 (4): 943–6. doi:10.1016/0091-3057(94)90300-X. 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. doi:10.4049/jimmunol.170.10.5118. PMID 12734358.
^ Stefano GB (2004). "Endogenous morphine: a role in wellness medicine". Med. Sci. Monit. 10 (6): ED5. PMID 15173675.
^ Chen, Wency (2012). "Opiate-induced constipation related to activation of small intestine opioid μ2-receptors". World Journal of Gastroenterology 18 (12): 1391–6. doi:10.3748/wjg.v18.i12.1391. PMC 3319967. PMID 22493554.
^ Liao D, Lin H, Law PY, Loh HH (February 2005). "Mu-opioid receptors modulate the stability of dendritic spines". Proc. Natl. Acad. Sci. U.S.A. 102 (5): 1725–30. Bibcode:2005PNAS..102.1725L. doi:10.1073/pnas.0406797102. JSTOR 3374498. PMC 545084. PMID 15659552.
^ Liu X-Y, Liu Z-C, Sun Y-G, Ross M, K S, Tsai F-F, Li Q-F, Jeffry J, Kim J-Y, Loh HH, Chen Z-F. "Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids". Cell 147 (2): 447–458. doi:10.1016/j.cell.2011.08.043. PMC 3197217. PMID 22000021. Lay summary – Washington University in St. Louis Press Release.
^ Martini L, Whistler JL (October 2007). "The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence". Current Opinion in Neurobiology 17 (5): 556–64. doi:10.1016/j.conb.2007.10.004. PMID 18068348.
^ Zuo Z (September 2005). "The role of opioid receptor internalization and beta-arrestins in the development of opioid tolerance". Anesthesia and Analgesia 101 (3): 728–34, table of contents. doi:10.1213/01.ANE.0000160588.32007.AD. PMID 16115983.
^ Marie N, Aguila B, Allouche S (November 2006). "Tracking the opioid receptors on the way of desensitization". Cellular Signalling 18 (11): 1815–33. doi:10.1016/j.cellsig.2006.03.015. PMID 16750901.
^ DuPen A, Shen D, Ersek M (September 2007). "Mechanisms of opioid-induced tolerance and hyperalgesia". Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses 8 (3): 113–21. doi:10.1016/j.pmn.2007.02.004. PMID 17723928.
^ Garzón J, Rodríguez-Muñoz M, Sánchez-Blázquez P (May 2005). "Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter". Neuropharmacology 48 (6): 853–68. doi:10.1016/j.neuropharm.2005.01.004. PMID 15829256.
^ Hooks SB, Martemyanov K, Zachariou V (January 2008). "A role of RGS proteins in drug addiction". Biochemical Pharmacology 75 (1): 76–84. doi:10.1016/j.bcp.2007.07.045. PMID 17880927.
^ Sirohi S, Dighe SV, Walker EA, Yoburn BC (November 2008). "The analgesic efficacy of fentanyl: relationship to tolerance and mu-opioid receptor regulation". Pharmacology, Biochemistry, and Behavior 91 (1): 115–20. doi:10.1016/j.pbb.2008.06.019. PMC 2597555. PMID 18640146.
^ Lopez-Gimenez JF, Vilaró MT, Milligan G (November 2008). "Morphine desensitization, internalization, and down-regulation of the mu opioid receptor is facilitated by serotonin 5-hydroxytryptamine2A receptor coactivation". Molecular Pharmacology 74 (5): 1278–91. doi:10.1124/mol.108.048272. PMID 18703670.
^ Kraus J (2009). "Regulation of mu-opioid receptors by cytokines". Frontiers in Bioscience (Scholar Edition) 1: 164–70. doi:10.2741/e16. PMID 19482692.
^ García-Fuster MJ, Ramos-Miguel A, Rivero G, La Harpe R, Meana JJ, García-Sevilla JA (November 2008). "Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers". Neuroscience 157 (1): 105–19. doi:10.1016/j.neuroscience.2008.09.002. PMID 18834930.
^ Ueda H, Ueda M (2009). "Mechanisms underlying morphine analgesic tolerance and dependence". Frontiers in Bioscience 14: 5260–72. doi:10.2741/3596. PMID 19482614.

External links

"Opioid Receptors: μ". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
mu Opioid Receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 慢性疼痛の治療の概要 overview of the treatment of chronic pain
2. オピオイド使用障害：病態、薬理学、スクリーニング、評価、および診断 opioid use disorder epidemiology pharmacology screening assessment and diagnosis
3. オピオイド系薬剤を用いた癌疼痛のマネージメント：至適鎮痛作用 cancer pain management with opioids optimizing analgesia
4. 術後疼痛のマネージメント management of postoperative pain
5. 妊娠時のブプレノルフィン補充療法 buprenorphine substitution therapy in pregnancy

English Journal

Antidepressant-like effects of 3-carboxamido seco-nalmefene (3CS-nalmefene), a novel opioid receptor modulator, in a rat IFN-α-induced depression model.

Callaghan CK1, Rouine J2, Dean RL3, Knapp BI4, Bidlack JM4, Deaver DR3, O'Mara SM2.
Brain, behavior, and immunity.Brain Behav Immun.2018 Jan;67:152-162. doi: 10.1016/j.bbi.2017.08.016. Epub 2017 Aug 24.
PMID 28844812

Genetic addiction risk score (GARS) ™, a predictor of vulnerability to opioid dependence.

Blum K1, Chen ALC2, Thanos PK3, Febo M4, Demetrovics Z5, Dushaj K6, Kovoor A7, Baron D8, Smith DE9, Roy III AK10, Fried L11, Chen TJH12, Chapman E Sr13, Modestino EJ14, Steinberg B14, Badgaiyan RD15.
Frontiers in bioscience (Elite edition).Front Biosci (Elite Ed).2018 Jan 1;10:175-196.
PMID 28930612

Tianeptine is associated with lower risk of suicidal ideation worsening during the first weeks of treatment onset compared with other antidepressants: A naturalistic study.

Nobile B1, Jaussent I2, Gorwood P3, Lopez Castroman J4, Olié E5, Guillaume S5, Courtet P5.
Journal of psychiatric research.J Psychiatr Res.2018 Jan;96:167-170. doi: 10.1016/j.jpsychires.2017.10.007. Epub 2017 Oct 16.
PMID 29073492

Japanese Journal

Haplotype block structure of the genomic region of the mu opioid receptor gene

Levran Orna,Awolesi Olaoluwakitan,Linzy Shirley [他]
Journal of human genetics 56(2), 147-155, 2011-02
NAID 40018281890

Involvement of the mu-opioid receptor in opioid tolerance induced by the intermittent administration of fentanyl in a rat chronic neuropathic pain model

Yoshimatsu Takashi,Moriyama Kumi,Iwao Yasuhide,Yorozu Tomoko,Iijima Takehiko
杏林医学会雑誌 42(2), 63-69, 2011
… This study examined the relationship between the opioid tolerance induced by high-dose fentanyl and the expression of the mu-opioid receptor (MOR) using the loose sciatic nerve ligation in rats. …
NAID 130001055558

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★リンクテーブル★

リンク元	「μオピオイド受容体」「mu receptor」「μオピオイドレセプター」
関連記事	「opioid」「mU」「mu」

「μオピオイド受容体」

Opioid receptor, mu 1
Identifiers
Symbols	OPRM1 ; LMOR; M-OR-1; MOP; MOR; MOR1; OPRM
External IDs	OMIM: 600018 MGI: 97441 HomoloGene: 37368 IUPHAR: 319 ChEMBL: 233 GeneCards: OPRM1 Gene
Gene ontology
Molecular function	• G-protein alpha-subunit binding; • G-protein coupled receptor activity; • beta-endorphin receptor activity; • voltage-gated calcium channel activity; • protein binding; • G-protein beta-subunit binding; • morphine receptor activity; • neuropeptide binding;
Cellular component	• endoplasmic reticulum; • Golgi apparatus; • cytosol; • plasma membrane; • integral component of plasma membrane; • neuron projection;
Biological process	• G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • adenylate cyclase-activating dopamine receptor signaling pathway; • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway; • negative regulation of adenylate cyclase activity; • phospholipase C-activating G-protein coupled receptor signaling pathway; • positive regulation of cytosolic calcium ion concentration; • neuropeptide signaling pathway; • synaptic transmission; • sensory perception; • locomotory behavior; • negative regulation of cell proliferation; • sensory perception of pain; • cellular response to stress; • opioid receptor signaling pathway; • positive regulation of cAMP-mediated signaling; • negative regulation of cAMP-mediated signaling; • negative regulation of nitric oxide biosynthetic process; • positive regulation of nitric oxide biosynthetic process; • behavioral response to ethanol; • positive regulation of neurogenesis; • negative regulation of cytosolic calcium ion concentration; • negative regulation of Wnt protein secretion; • positive regulation of ERK1 and ERK2 cascade; • calcium ion transmembrane transport; • cellular response to morphine; • regulation of N-methyl-D-aspartate selective glutamate receptor activity;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;