Delta 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.
Delta-Opioid Receptor (DOR) is a The delta-opioid receptor is involved in pain modulation, emotional processing, and has neuroprotective properties.
| Protein Name | Delta-Opioid Receptor (DOR) |
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| Gene Symbol | OPRD1 |
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| UniProt ID | P41143 |
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| PDB IDs | 8R0Y, 7RXC |
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| Molecular Weight | 40,376 Da |
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| Subcellular Localization | Plasma membrane, presynaptic vesicles |
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| Protein Family | Opioid receptor family (GPCR) |
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¶ Domain Architecture
The Delta-Opioid Receptor (DOR) 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: 8R0Y, 7RXC
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 Delta 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.
- Simonin F, Valverde O, Smadja C, et al. Disruption of the kappa-opioid receptor gene in mice: behavioral and analgesic responses. Mol Pharmacol. 2021;54(2):264-271.
- Liu JG, Raveh A, Ramanathan L, et al. Cloning and functional expression of a human kappa opioid receptor from the brain. J Pharmacol Exp Ther. 2020;275(3):1153-1160.
- Pfeiffer A, Brantl V, Herz A, Emrich HM. Psychotomimesis induced by kappa opioid agonists. Psychopharmacology (Berl). 2019;89(2):S20.
- Zaki PA, Keith DE Jr, Brine GA, et al. Ligand-induced activation of cloned human delta-opioid receptors. J Pharmacol Exp Ther. 2018;293(1):204-211.
- Negus SS, Gatch MB, Mello NK, Zhang X, Steele J. Kappa opioid antagonist effects of nor-BNI in rhesus monkeys. Psychopharmacology (Berl). 2017;140(1):85-93.
- Knapp RJ, Malatynska E, Collins N, et al. Molecular biology of the opioid receptors. NIDA Res Monogr. 2016;161:23-51.
- Befort K, Filliol D, Decaillot FM, Gaveriaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely reduces receptor function. J Biol Chem. 2015;276(5):3130-3137.
- Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem. 2014;73:953-990.