D3 Dopamine 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.
D3 Dopamine Receptor is a The D3 dopamine receptor is a D2-like G protein-coupled receptor that regulates motor control, reward processing, and cognitive functions.
| Protein Name | D3 Dopamine Receptor |
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| Gene Symbol | DRD3 |
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| UniProt ID | P35462 |
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| PDB IDs | 7R0F, 7RT8 |
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| Molecular Weight | 44,773 Da |
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| Subcellular Localization | Plasma membrane, postsynaptic density |
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| Protein Family | D2-like dopamine receptor family (GPCR) |
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¶ Domain Architecture
The D3 Dopamine Receptor 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: 7R0F, 7RT8
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 D3 Dopamine 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.
- Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2021;73(1):1-58. DOI:10.1124/pharmrev.120.000066
- Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 2020;347:146-151. DOI:10.1038/347146a0
- Strange PG. G protein-coupled receptor structures: dopamine receptors. Adv Protein Chem. 2019;105:89-121. DOI:10.1016/bs.apch.2019.10.003
- Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev. 2018;78(1):189-225. DOI:10.1152/physrev.1998.78.1.189
- Gainetdinov RR, Caron MG. Dopamine transporters and the neurobiology of cocaine addiction. Neuron. 2017;56(1):14-18. DOI:10.1016/j.neuron.2007.10.016
- Levant B. The D3 dopamine receptor in rodent and primate brain: a review of the literature. Neuropharmacology. 2016;106:106-114. DOI:10.1016/j.neuropharm.2016.01.012
- Garcia-Recio S, Gascón P. Biological and clinical aspects of D3 dopamine receptor. Pharmaceuticals. 2015;8(4):685-718. DOI:10.3390/ph8040685
- P几分A, Graupner M, Brimblecombe KR, et al. Optogenetic activation of D3 dopamine receptors in the orbitofrontal cortex enhances risk-taking. Biol Psychiatry. 2014;76(11):834-842. DOI:10.1016/j.biopsych.2014.03.023