μ receptor

Target id: 319

Nomenclature: μ receptor

Family: Opioid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 400 6q24-q25 OPRM1 opioid receptor mu 1 154
Mouse 7 398 10 A2 Oprm1 opioid receptor, mu 1 94
Rat 7 398 1p11 Oprm1 opioid receptor, mu 1 24,40,136,153,163
Previous and Unofficial Names
MOR-1
OP3
MOR
Mu opioid receptor
opioid receptor B
MOPr
opioid receptor, mu 1
opioid receptor
Database Links
Specialist databases
GPCRDB oprm_human (Hs), oprm_mouse (Mm), oprm_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NeXtProt
OMIM
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the mu-opioid receptor bound to a morphinan antagonist
PDB Id:  4DKL
Ligand:  β-FNA
Resolution:  2.8Å
Species:  Mouse
References:  82
Natural/Endogenous Ligands
dynorphin A-(1-13) {Sp: Human, Mouse, Rat}
dynorphin A {Sp: Human, Mouse, Rat}
dynorphin A-(1-8) {Sp: Human, Mouse, Rat}
dynorphin B {Sp: Human, Mouse, Rat}
endomorphin-1 {Sp: Human}
β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse} , β-endorphin {Sp: Rat}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
Comments: β-Endorphin is the highest potency endogenous ligand
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Met]enkephalin (PENK, P01210), [Leu]enkephalin (PENK, P01210), endomorphin-1, endomorphin-2

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]DAMGO Rn Full agonist 9.2 pKd 118
pKd 9.2 (Kd 5.7x10-10 M) [118]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 140
pKi 10.0 [140]
butorphanol Hs Partial agonist 9.9 pKi 42
pKi 9.9 (Ki 1.2x10-10 M) [42]
Description: Displacement of [3H]DAMGO from human μ opioid receptor expressed in CHO cells.
sufentanil Hs Full agonist 9.9 pKi 149
pKi 9.9 (Ki 1.38x10-10 M) [149]
etonitazene Hs Full agonist 9.7 pKi 140
pKi 9.7 [140]
hydromorphone Hs Agonist 9.6 pKi 155
pKi 9.6 (Ki 2.8x10-10 M) [155]
ethylketocyclazocine Hs Full agonist 9.5 pKi 140
pKi 9.5 [140]
etorphine Hs Full agonist 9.5 pKi 140
pKi 9.5 [140]
fentanyl Rn Full agonist 9.4 pKi 118
pKi 9.4 [118]
DAMGO Hs Full agonist 9.3 pKi 52,140
pKi 9.3 [52,140]
loperamide Hs Agonist 9.3 pKi 25
pKi 9.3 (Ki 5.3x10-10 M) [25]
(-)-methadone Hs Full agonist 9.2 pKi 140
pKi 9.2 [140]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 9.2 pKi 118
pKi 9.2 [118]
fentanyl Hs Full agonist 9.2 pKi 140
pKi 9.2 [140]
cebranopadol Hs Agonist 9.1 pKi 78
pKi 9.1 (Ki 7x10-10 M) [78]
Description: Radioligand binding assay
sufentanil Rn Full agonist 9.1 pKi 157
pKi 9.1 (Ki 7.7x10-10 M) [157]
eluxadoline Rn Agonist 9.1 pKi 17
pKi 9.1 (Ki 9x10-10 M) [17]
morphine Hs Full agonist 9.0 pKi 47,140
pKi 9.0 [47,140]
β-endorphin {Sp: Human} Rn Full agonist 9.0 pKi 118
pKi 9.0 [118]
PZM21 Hs Biased agonist 9.0 pKi 83
pKi 9.0 (Ki 1.1x10-9 M) [83]
dihydromorphine Hs Full agonist 8.8 pKi 140
pKi 8.8 [140]
dynorphin-(1-11) Hs Full agonist 8.8 pKi 140
pKi 8.8 [140]
normorphine Hs Full agonist 8.8 pKi 140
pKi 8.8 [140]
nalbuphine Hs Agonist 8.8 pKi 155
pKi 8.8 (Ki 1.6x10-9 M) [155]
buprenorphine Hs Partial agonist 8.8 pKi 140
pKi 8.8 [140]
eluxadoline Hs Agonist 8.8 pKi 17
pKi 8.8 (Ki 1.7x10-9 M) [17]
DADLE Hs Full agonist 8.7 pKi 140
pKi 8.7 [140]
DAMGO Rn Full agonist 8.7 pKi 118
pKi 8.7 [118]
hydrocodone Hs Agonist 8.7 pKi 107
pKi 8.7 (Ki 2x10-9 M) [107]
BU08028 Hs Partial agonist 8.7 pKi 65
pKi 8.7 (Ki 2.14x10-9 M) [65]
cebranopadol Rn Agonist 8.6 pKi 78
pKi 8.6 (Ki 2.4x10-9 M) [78]
Description: Radioligand binding assay
dynorphin B {Sp: Human, Mouse, Rat} Hs Full agonist 8.5 pKi 140
pKi 8.5 [140]
endomorphin-2 {Sp: Human} Rn Full agonist 8.5 pKi 162
pKi 8.5 (Ki 3.24x10-9 M) [162]
(-)-pentazocine Hs Partial agonist 8.4 pKi 140
pKi 8.4 [140]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Full agonist 8.4 pKi 140
pKi 8.4 [140]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 pKi 140
pKi 8.3 [140]
endomorphin-1 {Sp: Human} Hs Full agonist 8.3 pKi 49,162
pKi 8.3 [49,162]
DSLET Hs Full agonist 8.2 pKi 140
pKi 8.2 [140]
PL017 Hs Full agonist 8.2 pKi 22,140
pKi 8.2 [22,140]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 pKi 140
pKi 8.1 [140]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.1 pKi 140
pKi 8.1 [140]
UFP-512 Hs Agonist 8.0 pKi 148
pKi 8.0 [148]
Description: Measuring displacement of [3H]-diprenorphine in vitro
morphine Rn Partial agonist 7.9 pKi 118
pKi 7.9 [118]
BW373U86 Rn Agonist 7.8 pKi 21
pKi 7.8 (Ki 1.5x10-8 M) [21]
ADL5747 Hs Agonist 7.7 pKi 74
pKi 7.7 (Ki 1.8x10-8 M) [74]
ADL5859 Hs Agonist 7.5 pKi 73
pKi 7.5 (Ki 3.2x10-8 M) [73]
SCH221510 Hs Agonist 7.2 pKi 147
pKi 7.2 (Ki 6.5x10-8 M) [147]
Description: Radioligand binding assay
SR16835 Hs Agonist 7.1 pKi 141
pKi 7.1 (Ki 7.99x10-8 M) [141]
Description: Radioligand binding assay
codeine Hs Full agonist 6.9 pKi 140
pKi 6.9 [140]
tapentadol Hs Agonist 6.8 pKi 143
pKi 6.8 (Ki 1.6x10-7 M) [143]
BW373U86 Hs Agonist 6.6 pKi 73
pKi 6.6 (Ki 2.6x10-7 M) [73]
HS665 Hs Agonist 6.3 pKi 131
pKi 6.3 (Ki 5.42x10-7 M) [131]
compound 3 [PMID: 23134120] Hs Agonist 6.1 pKi 131
pKi 6.1 (Ki 8.26x10-7 M) [131]
tramadol Hs Agonist 5.8 pKi 155
pKi 5.8 (Ki 1.6x10-6 M) [155]
Description: Displacement of the mu aginist peptide DAMGO from the mu receptor expressed in CHO cells.
PZM21 Hs Biased agonist 8.3 pEC50 83
pEC50 8.3 (EC50 4.6x10-9 M) [83]
Description: In a Gi/o activation assay.
levorphanol Hs Agonist 9.9 pIC50 54
pIC50 9.9 (IC50 1.3x10-10 M) [54]
methadone Hs Agonist 8.4 pIC50 117
pIC50 8.4 (IC50 4.1x10-9 M) [117]
Description: Binding affinity against μ-opioid receptor (human) using [3H]DAMGO radioligand.
pethidine Hs Agonist 6.5 pIC50 117
pIC50 6.5 (IC50 3.15x10-7 M) [117]
AR-M1000390 Hs Agonist 5.4 pIC50 4
pIC50 5.4 (IC50 3.8x10-6 M) [4]
[3H]PL017 Rn Agonist - - 55
[55]
U-47700 Rn Agonist - - 26
[26]
View species-specific agonist tables
Agonist Comments
pKi values were determined in the absence of Na+ and guanine nucleotides.

Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγ35S binding in cell lines expressing cloned human mu receptors. Agents giving 85% or greater stimulation than that given by DAMGO have been characterized as Full Agonists [140].

It is still unclear whether endomorphins are endogenous. Morphine occurs endogenously [116].

We have tagged the μ receptor as the primary drug target for hydrocodone based on this drug having the highest affinity at this receptor compared to the κ and δ receptors [107]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [155].

Methadone is selective for the μ receptor: comparable IC50s at the κ and δ receptors are 512 and 1090nM respectively [117].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]diprenorphine Mm Antagonist 10.1 pKd 118
pKd 10.1 [118]
[3H]naloxone Mm Antagonist 9.0 pKd 118
pKd 9.0 [118]
naloxonazine Mm Antagonist 10.3 pKi 118
pKi 10.3 [118]
diprenorphine Mm Antagonist 10.1 pKi 118
pKi 10.1 [118]
quadazocine Hs Antagonist 10.0 pKi 140
pKi 10.0 [140]
(-)-bremazocine Hs Antagonist 9.7 pKi 140
pKi 9.7 [140]
CTOP Hs Antagonist 9.7 pKi 118
pKi 9.7 [118]
nalmefene Hs Antagonist 9.5 pKi 140
pKi 9.5 [140]
β-FNA Hs Antagonist 9.5 pKi 140
pKi 9.5 [140]
β-FNA Mm Antagonist 9.5 pKi 118
pKi 9.5 [118]
naltrexone Hs Antagonist 9.1 – 9.7 pKi 64,140
pKi 9.1 – 9.7 (Ki 7.1x10-10 – 1.99x10-10 M) [64,140]
GSK1521498 Hs Antagonist 9.4 pKi 64
pKi 9.4 (Ki 4.17x10-10 M) [64]
alvimopan Hs Antagonist 9.3 pKi 72
pKi 9.3 (Ki 4.7x10-10 M) [72]
diprenorphine Hs Antagonist 9.1 pKi 140
pKi 9.1 [140]
levallorphan Hs Antagonist 8.8 – 9.3 pKi 81
pKi 8.8 – 9.3 (Ki 1.69x10-9 – 4.8x10-10 M) [81]
Description: Competition binding assay- the calculated Ki varies depending on the radioligand used.
naloxone Mm Antagonist 9.0 pKi 118
pKi 9.0 [118]
nalorphine Hs Antagonist 8.9 pKi 140
pKi 8.9 [140]
naloxone Hs Antagonist 8.9 pKi 140
pKi 8.9 [140]
BNTX Hs Antagonist 8.8 pKi 140
pKi 8.8 [140]
AT-076 Hs Antagonist 8.8 pKi 164
pKi 8.8 (Ki 1.67x10-9 M) [164]
Description: Radioligand binding assay
methylnaltrexone Hs Antagonist 8.7 pKi 155
pKi 8.7 (Ki 2x10-9 M) [155]
Description: Displacement of [3H]DAMGO from human μ opioid receptors expressed in CHO cells
CTAP Hs Antagonist 8.6 pKi 22,140
pKi 8.6 [22,140]
naloxone benzoylhydrazone Hs Antagonist 8.2 – 8.7 pKi 140
pKi 8.7 [140]
pKi 8.2 [140]
naltrindole Hs Antagonist 8.2 pKi 140
pKi 8.2 [140]
naltriben Hs Antagonist 7.9 pKi 140
pKi 7.9 [140]
nor-binaltorphimine Hs Antagonist 7.7 pKi 140
pKi 7.7 [140]
LY2456302 Hs Antagonist 7.6 pKi 120
pKi 7.6 (Ki 2.4x10-8 M) [120]
zyklophin Hs Antagonist 5.2 pKi 110
pKi 5.2 (Ki 5.88x10-6 M) [110]
View species-specific antagonist tables
Antagonist Comments
β-FNA is an electrophilic affinity label. The pKi reflects both the reversible and irreversible binding components.
CTOP is a good somatostatin receptor (sst receptor) agonist in addition to having antagonist activity at μ opioid receptors; it should never be used in studies of μ receptor function in situations where sst receptors may be involved. CTAP does not activate sst receptors [30].

The μ receptor is tagged as the primary target for the drug levallorphan, since the drug is mainly used for its antagonistic actions as an antidote to opioid overdose. Note that this drug also acts as a partial agonist at the κ receptor.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BMS-986123 Hs Neutral 6.0 pKB 18
pKB 6.0 (KB 1x10-6 M) [18]
BMS-986121 Hs Positive 5.7 pKB 18
pKB 5.7 (KB 2x10-6 M) [18]
BMS-986124 Hs Neutral 5.7 pKB 18
pKB 5.7 (KB 2x10-6 M) [18]
BMS-986122 Hs Positive 5.3 pKB 18
pKB 5.3 (KB 5x10-6 M) [18]
BMS-986121 Hs Positive 6.0 pEC50 18
pEC50 6.0 (EC50 1x10-6 M) [18]
BMS-986122 Hs Positive 5.5 pEC50 18
pEC50 5.5 (EC50 3x10-6 M) [18]
Allosteric Modulator Comments
BMS-986123 and BMS-986124 are Silent Allosteric Modulators (SAMs). These compounds neither potentiate nor inhibit the actions of an orthosteric agonist, however they block the actions of the Positive Allosteric Modulators (PAMs).
A number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate μ opioid receptor affinities and function. In addition sodium and guanyl nucleotides can modify the functional μ receptor complex and G protein interaction. Also, μ receptors are reported to form heterodimers with other receptors of the OP family or with non-opioid G protein-coupled receptors. Heterodimerisation may alter μ receptor function and/or trafficking [44,48,111].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase stimulation
Adenylate cyclase inhibition
Phospholipase C stimulation
Potassium channel
Calcium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  The following systems have also been reported to be activated following Gi/Go activation via the μ receptor:
  • Epidermal growth factor receptor transactivation and subsequent mitogen activated protein kinase ERK [11,77]
  • Jun N-terminal kinase (JNK) expression and activity [38,62,128]
  • Signal transducer and activator of transcription 3 (STAT3) [161]
  • Focal adhesion kinase [84]
  • Nuclear Ca2+/calmodulin translocation [150]
  • Phosphatidylinositol-3 kinase expression and activity [62,105].
References:  6,16,19-20,32,41,56,67,96,98,104,108,114-115,119,144,159
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  G16 couples to the μ opioid receptor and activates PLC.
References:  57,75
Tissue Distribution
Skin: dermal and epidermal nerve fibers.
Species:  Human
Technique:  Immunohistochemistry.
References:  132
Immune cells: CEM x174 T/B lymphocytes, Raji B cells, CD4+, monocytes/macrophages, neutrophils.
Species:  Human
Technique:  RT-PCR.
References:  31
Pregnant uterus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  165
CNS: caudate putamen, nucleus accumbens, endopiriform nucleus, fundus striati, habenula, amygdaloid nuclei, thalamus, hypothalamus, zona incerta, ventral tegmental area, interpeduncular nucleus, central gray, dentate gyrus, substantia nigra, the superior colliculus.
Species:  Mouse
Technique:  Radioligand binding.
References:  66
CNS: nucleus accumbens (plasma membranes: extrasynaptic neuronal > glial)
Species:  Rat
Technique:  immunocytochemistry.
References:  133
CNS: Olfactory bulb, striatal patches and subcallosal streak, medial septum, piriform and cingulate cortex, entorhinal cortex, bed nucleus stria terminalis, medial preoptic area, globus and ventral pallidum, thalamic nuclei, lateral hypothalamus, mammillary nuclei , hippocampus, amygdaloid nuclei, ventral and lateral periaqueductal grey, ventral tegmental area and substantia nigra pars compacta, superior and inferior colliculi, interpeduncular nuclei, locus ceruleus, parabrachial nuclei, median raphe, nucleus of the solitary tract, spinal cord (dorsal root ganglia and layers I and II).
Species:  Rat
Technique:  in situ hybridisation.
References:  136
CNS: olfactory bulb.
Species:  Rat
Technique:  immunocytochemistry.
References:  125
CNS: cerebral cortex, striatum, hippocampus, locus coeruleus, superficial laminae of the dorsal horn.
Species:  Rat
Technique:  Immunohistochemistry.
References:  5
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  7
CNS: superficial layers of the dorsal horn.
Species:  Rat
Technique:  immunocytochemistry.
References:  28-29
CNS: striatum, medial habenular nucleus, medial terminal nucleus of the accessory optic tract, interpeduncular nucleus, median raphe nucleus, parabrachial nuclei, locus coeruleus, ambiguous nucleus, nucleus of the solitary tract, and laminae I and II of the medullary and spinal dorsal horns, cerebral cortex, amygdala, thalamus, and hypothalamus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  35
CNS: striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus.
Species:  Rat
Technique:  Radioligand binding.
References:  135
CNS: nucleus accumbens (plasma membranes of GABAergic neurons).
Species:  Rat
Technique:  immunocytochemistry.
References:  134
CNS: superficial layers of the medullary and spinal dorsal horns. Colocalisation with substance P.
Species:  Rat
Technique:  immunocytochemistry.
References:  36,76
CNS: caudate putamen.
Species:  Rat
Technique:  immunocytochemistry.
References:  63,151
CNS: superficial layers of the spinal cord dorsal horn, nucleus caudalis of the spinal tract of the trigeminal, nucleus of the solitary tract, nucleus ambiguous, locus coeruleus, interpeduncular nucleus, lateral habenular nucleus, caudate-putamen, nucleus accumbens, ventral tegmental area, thalamus, hypothalamus, amygdaloid nuclei, nucleus accumbens, cerebral cortex, septum and diagonal band, preoptic area, medial thalamic and habenular nuclei, locus coeruleus, nucleus ambiguous, trigeminal nucleus caudalis, spinal cord substantia gelatinosa zones.
Species:  Rat
Technique:  Immunohistochemistry.
References:  101
CNS: locus coeruleus (noradrenergic perikarya and dendrites).
Species:  Rat
Technique:  immunocytochemistry.
References:  145-146
CNS: accessory olfactory bulb, striatal patches and streaks, amygdaloid nuclei, ventral hippocampal subiculum and dentate gyrus, numerous thalamic nuclei, geniculate bodies, central grey, superior and inferior colliculi, solitary and pontine nuclei and substantia nigra.
Species:  Rat
Technique:  Radioligand binding.
References:  126
CNS: thalamus, striosomes of the caudate-putamen, globus pallidus, cerebral cortex.
Species:  Rat
Technique:  in situ hybridisation.
References:  34
CNS: thalamic, brainstem and reticular core nuclei (highest in the habenular and thalamic nuclei).
Species:  Rat
Technique:  in situ hybridisation.
References:  45
CNS: accessory olfactory bulb, anterior olfactory nuclei, striatal patches of the nucleus accumbens and caudate-putamen, endopiriform nucleus, claustrum, diagonal band of Broca, globus pallidus, ventral pallidum, bed nucleus of stria terminalis, most thalamic nuclei, medial and posteriocortical medial amygdala, lateral, dorsomedial, posterior and mammillary nuclei of the hypothalamus, presubiculum, subiculum, rostral interpeduncular nucleus, median raphe, inferior colliculus, parabrachial nucleus, locus coeruleus, central grey, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis, nucleus cuneatus, dorsal motor nucleus of vagus.
Species:  Rat
Technique:  In situ hybridisation and radioligand binding.
References:  87
CNS: thalamus, striatum, hypothalamus and pons-medulla > hippocampus and midbrain > cerebral cortex and cerebellum.
Species:  Rat
Technique:  Northern blotting.
References:  95
CNS: olfactory bulb, caudate-putamen, nucleus accumbens, lateral and medial septum, diagonal band of Broca, bed nucleus of the stria terminalis, most thalamic nuclei, hippocampus, amygdala, medial preoptic area, superior and inferior colliculi, central gray, dorsal and median raphe, raphe magnus, locus coeruleus, parabrachial nucleus, pontine and medullary reticular nuclei, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis and cuneatus, dorsal motor nucleus of vagus, spinal cord, dorsal root ganglia.
Species:  Rat
Technique:  in situ hybridisation.
References:  86
CNS: superficial layers (laminae I and II) of the dorsal horn of the spinal cord.
Species:  Rat
Technique:  Radioligand binding.
References:  13
Accessory optic tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  37
CNS: Purkinje cells and granular and molecular layers of the fetal, neonatal and adult cerebellum.
Species:  Rat
Technique:  Immunohistochemistry.
References:  102
Ear: cochleae.
Species:  Rat
Technique:  RT-PCR.
References:  61,112
CNS: anterior cingulate cortex, neocortex, amygdala, hippocampus, ventral dentate gyrus, presubiculum, nucleus accumbens, caudate putamen, thalamus, habenula, interpeduncular nucleus, pars compacta of the substantia nigra, superior and inferior colliculi, raphe nuclei.
Species:  Rat
Technique:  Radioligand binding.
References:  88
Tissue Distribution Comments
μ opioid receptors are widely distributed with dense labelling throughout the fore, mid and hindbrain regions in the CNS. Quantitatively, the μ receptor is the most highly expressed of all the opioid receptors. Although the early studies used non-selective ligands such as [3H]dihydromorphine, characterisation of the distribution of the μ opioid receptor has been aided by the availability of [3H]DAMGO, a highly selective opioid agonist that has been the ligand of choice for labelling μ opioid receptors for over 20 years. Immunohistochemistry has largely confirmed receptor autoradiography.

For a review of μ opioid receptor expression in the rat see [85].
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of intracellular cAMP levels in SH-SY5Y cells endogenously expressing the μ receptor.
Species:  Human
Tissue:  SH-SY5Y cells.
Response measured:  Inhibition of cAMP accumulation.
References:  160
Measurement of [35S]GTPγS binding.
Species:  Rat
Tissue:  Brain slices.
Response measured:  [35S]GTPγS binding.
References:  127
Physiological Functions
Constriction of the pupil.
Species:  Human
Tissue:  Pupil.
References:  103
DAMGO increases the conductance of an inwardly rectifying potassium conductance and hyperpolarises locus coeruleus neurons.
Species:  Rat
Tissue:  Brain.
References:  108
μ receptor agonsts reduce bith early (GABAA receptor-mediated) and late (GABAB receptor-mediated) inhibitory postsynaptic currents in the dentate gyrus of hippocampal slices.
Species:  Rat
Tissue:  Hippocampal slices.
References:  156
Morphine inhibits N- and P/Q-type Ca2+ channels in the nucleus traxtus solitarius of the rat.
Species:  Rat
Tissue:  Brain.
References:  119
Morphine is responsible for modulating the Ca2+ currents in the mouse periaqueductal grey neurons.
Species:  Mouse
Tissue:  Periaqueductal grey neurons.
References:  32
Morphine inhibits interpheron (IFN)-γ promotor activity in activated mouse T cells, which is mediated through two distinct cAMP-dependent pathways, the NF-κB signalling pathway and the ERK1/2, p38 MAPK, AP-1/NFAT pathway.
Species:  Mouse
Tissue:  T cells.
References:  152
Body temperature regulation:
μ receptor activation induces hypothermia, blocked by selective μ receptor antagonists. The effect is centrally mediated, involving both oxidative metabolism and heat exchange.
Species:  Rat
Tissue:  In vivo.
References:  53
Physiological Consequences of Altering Gene Expression
Analgesia:
Untreated μ receptor knockout mice display shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice, which support the role for endogenous opioid-peptide interactions with the μ receptor in normal nociceptive processing. Interestingly, analgesia produced by the δ opioid receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) in hot plate and tail flick tests is dramatically reduced in μ opioid receptor knockout mice in a gene-dose-dependent fashion, suggesting that DPDPE may require μ opioid receptor occupancies for full efficacy.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  79,89,123,129-130
Analgesia:
Loss of μ opioid receptors prevents the plasma membrane translocation of δ opioid receptors in the dorsal horn of the spinal cord caused by chronic inflammatory pain induced by intraplantar injection of Freund's adjuvant.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  99-100
Addictions; drug-induced reinforcement:
Opioid self-administration is abolished in μ receptor knockout mice. On the contrary, morphine is aversive in the μ opioid deficient mice by interaction with κ opioid receptors. In addition, μ opioid receptors may play a role in mediating various addictive agents such as ethanol, cocaine, nicotine and cannabinoid. Ethanol consumption is decreased in μ opioid knockout mice, and the animals exhibit less ethanol reward in a conditioned place preference paradigm.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8-9,12,33,46,50-51,58
Addictions; locomotor activity:
Cocaine-induced locomotor activity but not sensitisation is abolished in μ receptor knockout mice, while wild-type and heterozygous μ receptor mice display reduced cocaine conditioned place-preference, confirming a central role of μ receptors in drug reward but opposing effects in locomotor sensitisation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  158
Emotional responsivity:
μ opioid receptors may play a role in the modification of emotional responses to novelty, anxiety and depression. μ receptor knockout mice show less anxiety in the elevated plus maze and emergence tests, reduced response to novel stimuli in the novelty test and less depressive-like behaviour in the forced swim test.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  39
Attachment behaviour:
Pups of μ receptor knockout mice emit fewer ultrasonic vocalisations when removed from their mothers. It indicates a role for μ opioid receptors in diseases characterised by deficits in attachment behaviour, such as autism or reactive attachment disorder.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  97
Modulation of neurotransmitter systems, dopamine:
Administration of apomorphine increases the locomotor activity of μ receptor knockout mice more than wild-type mice, which may be related to the increased binding sites of the dopamine D2 receptor in the caudate putamen of receptor deficient mice. A tonically active μ opioid system modulates the basal dopamine neurotransmission in the nucleus accumbens (NAc). Microdialysis studies have revealed significant decreases in the dopamine fraction in μ opioid receptor knckout mice. μ opioid receptor knockout mice show diminished food-anticipatory activity which is dependent on μ-regulated dopaminergic activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  23,139
Modulation of neurotransmitter systems, acetylcholine:
Muscarinic M1 receptor mRNA and protein levels are reduced in various bran regions when compared to the wild-type. In μ opioid receptor deficient mice an up-regulation of acetylcholinesterase activity and compensatory down-regulation of M2 muscarinic receptors in the striatal caudate putamen and nucleus accumbens have been reported, which can be associated with the enhanced tremors after administration of acetylcholinesterase inhibitors.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  138
Modulation of neurotransmitter systems, glutamate, somatostatin:
An increase in glutamate and somatostatin binding was observed in μ receptor knockout mice, which may contribute to the enhanced excitability in these mice, showing an accelerated kindling development induced by the convulsant drug pentylenetetrazol.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  97
Learning and memory:
Several studies have demonstrated that the loss of μ opioid receptors decreases LTP in the dentate gyrus of the hippocampus, suggesting the possibility that the lack of μ opioid receptors may acccompany a change in learning and memory. μ opioid receptor knockout mice show a significant spatial memory impairment compared to wild-type in the Morris water maze. They also exhibit an impairment in the ultimate level of spatial learning, suggesting that the μ opioid receptor may play a positive role in learning and memory by increasing LTP in CA3 neurons. On the other hand, the learning deficit induced in pentylenetetrazol kindling id absent in μ opioid receptor knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  59-60,90
Immune responses:
In μ receptor knockout mice chronic morphine administration cannot induce lymphoid organ atrophy, nor diminish the ratio of CD4+ CD8+ cells in the thymus nor reduce natural killer activity. Morphine modulation of macrophage phagocytosis and macrophage secretion of TNFα is not observed in μ receptor knockout animals. In contrast, morphine reduction of splenic and thymic cell number and mitogen-induced proliferation are unaffected, as is morphine inhibition of Il-1 and Il-6 secretion by macrophages. Morphine treatment promotes T(H2) differentiation through a μ opioid dependent mechanism. Developing T cells are responsive to the chemotactic effect of μ opioid agonists, an effect not seen in μ opioid knockout mice. Deficiency of μ receptor exacerbates experimental colitis whereas administration of the μ receptor agonist DAMGO reduces inflammation in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  43,93,113,121-122
Other physiological functions:
Sexual function in male homozygotes is affected, as shown by reducing mating activity and a decrease in sperm count and motility. Morphine-induced inhibition of gastrointestinal transit is abolished in μ receptor knockout mice, and basal GI motility is lower as compared to heterozygous and wild-type animals. μ opioid receptor knockout mice develop insulin resistance more rapidly than wild-type mice indicating a role for μ in controlling insulin resistance.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27,137
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Oprm1tm1Jlw Oprm1tm1Jlw/Oprm1tm1Jlw
involves: 129P2/OlaHsd
MGI:97441  MP:0009748 abnormal behavioral response to addictive substance PMID: 18207746 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0009278 abnormal bone marrow cell physiology PMID: 9126934 
Oprm1+|Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1+
involves: Black Swiss
MGI:97441  MP:0009278 abnormal bone marrow cell physiology PMID: 9126934 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
MGI:97441  MP:0000188 abnormal circulating glucose level PMID: 16505249 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0006410 abnormal common myeloid progenitor cell morphology PMID: 9126934 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd * BALB/c * C57BL/6
MGI:97441  MP:0002912 abnormal excitatory postsynaptic potential PMID: 10727705 
Oprm1tm1Yxp Oprm1tm1Yxp/Oprm1tm1Yxp
involves: 129/Sv * C57BL/6
MGI:97441  MP:0006001 abnormal intestinal transit time PMID: 19273844 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0003959 abnormal lean body mass PMID: 19221053 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd * BALB/cJ * C57BL/6J
MGI:97441  MP:0003633 abnormal nervous system physiology PMID: 15893889 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0002803 abnormal operant conditional behavior PMID: 15355329 
Oprm1+|Oprm1tm1Jep Oprm1tm1Jep/Oprm1+
B6.129S-Oprm1
MGI:97441  MP:0002803 abnormal operant conditional behavior PMID: 15355329 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
MGI:97441  MP:0001970 abnormal pain threshold PMID: 10835636  8893006 
Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1tm1Uhl
involves: 129S7/SvEvBrd * C57BL/6J
MGI:97441  MP:0001970 abnormal pain threshold PMID: 9037090 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0008872 abnormal physiological response to xenobiotic PMID: 17544222 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd
MGI:97441  MP:0001463 abnormal spatial learning PMID: 14499482 
Oprm1tm2.1Loh Oprm1tm2.1Loh/Oprm1tm2.1Loh
Not Specified
MGI:97441  MP:0001968 abnormal touch/ nociception PMID: 12525693 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0002675 asthenozoospermia PMID: 9126934 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
MGI:97441  MP:0009776 decreased behavioral withdrawal response PMID: 10835636 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd
MGI:97441  MP:0001982 decreased chemically-elicited antinociception PMID: 9555078 
Oprm1+|Oprm1tm1Loh Oprm1tm1Loh/Oprm1+
involves: 129P2/OlaHsd
MGI:97441  MP:0001982 decreased chemically-elicited antinociception PMID: 9555078 
Oprm1tm1Yxp Oprm1tm1Yxp/Oprm1tm1Yxp
involves: 129/Sv * C57BL/6
MGI:97441  MP:0001982 decreased chemically-elicited antinociception PMID: 19273844 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0001982 decreased chemically-elicited antinociception PMID: 9126934 
Oprm1tm1Jabl Oprm1tm1Jabl/Oprm1tm1Jabl
C57BL/6-Oprm1
MGI:97441  MP:0001982 decreased chemically-elicited antinociception PMID: 19528658 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0001935 decreased litter size PMID: 9126934 
Oprm1+|Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1+
either: B6.129S7-Oprm1 or (involves: 129S7/SvEvBrd)
MGI:97441  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 11377918 
Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1tm1Uhl
involves: 129S7/SvEvBrd * C57BL/6J
MGI:97441  MP:0009767 decreased sensitivity to xenobiotic induced morbidity/mortality PMID: 11377918 
Oprm1+|Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1+
either: B6.129S7-Oprm1 or (involves: 129S7/SvEvBrd)
MGI:97441  MP:0009767 decreased sensitivity to xenobiotic induced morbidity/mortality PMID: 11377918 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd
MGI:97441  MP:0009767 decreased sensitivity to xenobiotic induced morbidity/mortality PMID: 9555078 
Oprm1+|Oprm1tm1Loh Oprm1tm1Loh/Oprm1+
involves: 129P2/OlaHsd
MGI:97441  MP:0009767 decreased sensitivity to xenobiotic induced morbidity/mortality PMID: 9555078 
Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1tm1Uhl
involves: 129S7/SvEvBrd * C57BL/6J
MGI:97441  MP:0003998 decreased thermal nociceptive threshold PMID: 9037090 
Oprm1tm1Jabl Oprm1tm1Jabl/Oprm1tm1Jabl
C57BL/6-Oprm1
MGI:97441  MP:0003998 decreased thermal nociceptive threshold PMID: 19528658 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0009749 enhanced behavioral response to addictive substance PMID: 15355329 
Oprm1+|Oprm1tm1Jep Oprm1tm1Jep/Oprm1+
B6.129S-Oprm1
MGI:97441  MP:0009749 enhanced behavioral response to addictive substance PMID: 15355329 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv
MGI:97441  MP:0009779 enhanced behavioral response to anesthetic PMID: 11032994 
Oprm1+|Oprm1tm1Jep Oprm1tm1Jep/Oprm1+
involves: 129S/SvEv
MGI:97441  MP:0009779 enhanced behavioral response to anesthetic PMID: 11032994 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd
MGI:97441  MP:0009754 enhanced behavioral response to cocaine PMID: 12781916 
Oprm1+|Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1+
either: B6.129S7-Oprm1 or (involves: 129S7/SvEvBrd)
MGI:97441  MP:0009713 enhanced conditioned place preference behavior PMID: 11377918 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0009171 enlarged pancreatic islets PMID: 19221053 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
MGI:97441  MP:0001402 hypoactivity PMID: 8893006 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0001402 hypoactivity PMID: 9126934 
Oprm1+|Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1+
involves: Black Swiss
MGI:97441  MP:0001402 hypoactivity PMID: 9126934 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0002578 impaired ability to fire action potentials PMID: 15926936 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv
MGI:97441  MP:0009778 impaired behavioral response to anesthetic PMID: 10195199  11032994 
Oprm1+|Oprm1tm1Jep Oprm1tm1Jep/Oprm1+
involves: 129S/SvEv
MGI:97441  MP:0009778 impaired behavioral response to anesthetic PMID: 10195199  11032994 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
involves: 129S2/SvPas
MGI:97441  MP:0009778 impaired behavioral response to anesthetic PMID: 10195199 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0009778 impaired behavioral response to anesthetic PMID: 17544222 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 8893006 
Oprm1tm1Uhl Oprm1tm1Uhl/Oprm1tm1Uhl
involves: 129S7/SvEvBrd * C57BL/6J
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 11377918 
Oprm1tm1Loh Oprm1tm1Loh/Oprm1tm1Loh
involves: 129P2/OlaHsd
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 12781916  9555078 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 9126934 
Oprm1+|Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1+
involves: Black Swiss
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 9126934 
Oprm1tm1Jabl Oprm1tm1Jabl/Oprm1tm1Jabl
C57BL/6-Oprm1
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 19528658 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 10195199  11032994 
Oprm1+|Oprm1tm1Jep Oprm1tm1Jep/Oprm1+
involves: 129S/SvEv
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 10195199  11032994 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
involves: 129S2/SvPas
MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 10195199 
Oprd1tm1Jep|Oprm1tm1Jep Oprd1tm1Jep/Oprd1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep,Oprm1tm1Jep/Oprm1tm1Jep
involves: 129S/SvEv * 129S2/SvPas
MGI:97438  MGI:97441  MP:0009757 impaired behavioral response to morphine PMID: 17544222 
Oprm1tm1Jabl Oprm1tm1Jabl/Oprm1tm1Jabl
C57BL/6-Oprm1
MGI:97441  MP:0009712 impaired conditioned place preference behavior PMID: 19528658 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0005292 improved glucose tolerance PMID: 19221053 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0001260 increased body weight PMID: 19221053 
Oprm1tm1Jlw Oprm1tm1Jlw/Oprm1tm1Jlw
involves: 129P2/OlaHsd
MGI:97441  MP:0001981 increased chemically-elicited antinociception PMID: 18207746 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0002079 increased circulating insulin level PMID: 19221053 
Oprm1tm1Kff Oprm1tm1Kff/Oprm1tm1Kff
129S2/SvPas
MGI:97441  MP:0003063 increased coping response PMID: 10835636 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0003135 increased erythroid progenitor cell number PMID: 9126934 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0003058 increased insulin secretion PMID: 19221053 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0009108 increased pancreas weight PMID: 19221053 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1
MGI:97441  MP:0005458 increased percent body fat PMID: 19221053 
Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1tm1Lyu
involves: Black Swiss
MGI:97441  MP:0009336 increased splenocyte proliferation PMID: 9126934 
Oprm1+|Oprm1tm1Lyu Oprm1tm1Lyu/Oprm1+
involves: Black Swiss
MGI:97441  MP:0009336 increased splenocyte proliferation PMID: 9126934 
Oprm1tm1Jep Oprm1tm1Jep/Oprm1tm1Jep
B6.129S-Oprm1