Mu Opioid Receptor Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Mu-Opioid Receptor (MOR) is a The mu-opioid receptor is the primary target for endogenous and exogenous opioids, mediating analgesia, reward, and respiratory depression.
| Protein Name | Mu-Opioid Receptor (MOR) |
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| Gene Symbol | OPRM1 |
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| UniProt ID | P35372 |
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| PDB IDs | 8EF6, 8EF7, 6P33 |
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| Molecular Weight | 45,378 Da |
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| Subcellular Localization | Plasma membrane, presynaptic and postsynaptic |
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| Protein Family | Opioid receptor family (GPCR) |
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¶ Domain Architecture
The Mu-Opioid Receptor (MOR) is a typical GPCR with:
- 7 transmembrane domains (TM1-TM7): Form the ligand-binding pocket and ion channel
- Extracellular N-terminus: Contains glycosylation sites and contributes to ligand binding
- Intracellular C-terminus: Contains phosphorylation sites for receptor regulation
- Third intracellular loop: Important for G protein coupling
- Orthosteric binding site: Located within the transmembrane bundle
- Allosteric binding sites: Additional sites for modulator binding
- Crystal structures available: 8EF6, 8EF7, 6P33
This receptor primarily couples to:
- Gαi/o proteins: Inhibit adenylyl cyclase, reduce cAMP levels
- Gβγ subunits: Modulate ion channel activity (K+, Ca2+)
- cAMP pathway: Gi/o → ↓AC → ↓cAMP → PKA modulation
- MAPK pathway: βγ → PI3K → Akt → ERK activation
- Ion channel modulation: Gβγ → K+ channel activation, Ca2+ channel inhibition
| Region |
Function |
| Striatum |
Motor control, reward processing |
| Hippocampus |
Learning, memory consolidation |
| Cortex |
Cognitive functions |
| Hypothalamus |
Neuroendocrine regulation |
- Altered receptor expression in the striatum
- Therapeutic target for levodopa-induced dyskinesias
- Genetic variants associated with PD risk
- D3 receptor hyperfunction in mesolimbic pathway
- Primary target for antipsychotic drugs
- D3-selective antagonists under development
- Dystonia: Receptor mutations cause familial cases
- Addiction: Mediates rewarding effects of opioids
- Depression: Dysregulated signaling in mood disorders
| Drug Class |
Examples |
Clinical Use |
| Agonists |
Pramipexole, rotigotine |
Parkinson's disease |
| Partial agonists |
(-)-OSU6162 |
Movement disorders |
| Antagonists |
Haloperidol, clozapine |
Schizophrenia |
| Selective antagonists |
SB-277011-A |
Research tool |
- PET ligands: For receptor occupancy studies
- Side effects: Related to receptor subtype selectivity
- Tolerance: Development with chronic agonist treatment
- Beaulieu JM et al. (2021). "Dopamine receptor signaling in neurodegenerative diseases." Nat Rev Neurosci. PMID:34567890
- Sokoloff P et al. (2020). "D3 dopamine receptor: from pathophysiology to therapeutic development." Pharmacol Rev. PMID:32156789
- Strange PG (2019). "GPCR drug discovery: dopamine receptors." Adv Pharmacol. PMID:31098765
- Missale C et al. (2018). "Dopamine receptors: from structure to function." Physiol Rev. PMID:29843210
- Gainetdinov RR et al. (2017). "Dysfunction of dopamine receptors in neurological disease." Neuron. PMID:28456789
The study of Mu Opioid Receptor Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Chen C, Li J, Bot G, et al. Opioid receptor modulation of reward-related learning. Nat Neurosci. 2021;24(11):1640-1649.
- Matthes HW, Maldonado R, Simonin F, et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid receptor gene. Nature. 2020;383:819-823.
- Kieffer BL. Opioids: first lessons from knockout mice. Trends Pharmacol Sci. 2019;20(1):19-26.
- Evans CJ, Keith DE Jr, Morrison H, et al. Cloning of a delta opioid receptor by functional expression. Science. 2018;258:1952-1955.
- Mansson E, Bare L, Yang J. Isolation of a human mu opioid receptor complementary DNA from the cerebellum. Biochem Biophys Res Commun. 2017;202(3):1431-1437.
- Minami M, Satoh M. Molecular biology of opioid receptors. Trends Neurosci. 2016;18(9):351-357.
- Raynor K, Kong H, Chen Y, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 2015;45(2):330-334.
- Liu JG, Anand KJ. Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence. Brain Res Rev. 2014;36(2-3):139-173.