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D3 receptor

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Target not currently curated in GtoImmuPdb

Target id: 216

Nomenclature: D3 receptor

Family: Dopamine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 400 3q13.31 DRD3 dopamine receptor D3 51
Mouse 7 446 16 28.44 cM Drd3 dopamine receptor D3 43
Rat 7 446 11q21 Drd3 dopamine receptor D3 133
Previous and Unofficial Names Click here for help
D3 receptor | dopamine D3 receptor | dopaminergic receptor D3 | D3R
Database Links Click here for help
Specialist databases
GPCRdb drd3_human (Hs), drd3_mouse (Mm), drd3_rat (Rn)
Other databases
Alphafold P35462 (Hs), P30728 (Mm), P19020 (Rn)
ChEMBL Target CHEMBL234 (Hs), CHEMBL3441 (Mm), CHEMBL3138 (Rn)
DrugBank Target P35462 (Hs)
Ensembl Gene ENSG00000151577 (Hs), ENSMUSG00000022705 (Mm), ENSRNOG00000060806 (Rn)
Entrez Gene 1814 (Hs), 13490 (Mm), 29238 (Rn)
Human Protein Atlas ENSG00000151577 (Hs)
KEGG Gene hsa:1814 (Hs), mmu:13490 (Mm), rno:29238 (Rn)
OMIM 126451 (Hs)
Orphanet ORPHA121179 (Hs)
Pharos P35462 (Hs)
RefSeq Nucleotide NM_000796 (Hs), NM_007877 (Mm), NM_017140 (Rn)
RefSeq Protein NP_000787 (Hs), NP_031903 (Mm), NP_058836 (Rn)
SynPHARM 2633 (in complex with eticlopride)
UniProtKB P35462 (Hs), P30728 (Mm), P19020 (Rn)
Wikipedia DRD3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human dopamine D3 receptor in complex with eticlopride
PDB Id:  3PBL
Ligand:  eticlopride
Resolution:  2.89Å
Species:  Human
References:  26
Natural/Endogenous Ligands Click here for help
dopamine

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Agonists
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Ligand Sp. Action Value Parameter Reference
[3H]7-OH-DPAT Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Agonist 9.6 pKd 121
⤷ pKd 9.6 (Kd 2.7x10-10 M) [121]
[3H]7-OH-DPAT Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Agonist 9.1 pKd 89
⤷ pKd 9.1 (Kd 7.94x10-10 M) [89]
[3H]PD128907 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Agonist 9.0 pKd 3
⤷ pKd 9.0 (Kd 9.9x10-10 M) [3]
cariprazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 10.1 pKi 68
⤷ pKi 10.1 (Ki 9x10-11 M) [68]
Description: Binding affinity to human dopamine D3 receptor
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 9.6 pKi 103
⤷ pKi 9.6 [103]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 9.1 pKi 103
⤷ pKi 9.1 [103]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 9.0 pKi 103
⤷ pKi 9.0 [103]
BP 897 Small molecule or natural product Hs Partial agonist 9.0 pKi 115
⤷ pKi 9.0 (Ki 1x10-9 M) [115]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.9 pKi 103
⤷ pKi 8.9 [103]
pramipexole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.4 – 8.7 pKi 98,124
⤷ pKi 8.4 – 8.7 [98,124]
(-)-N-porphynorapomorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.4 – 8.7 pKi 44,124
⤷ pKi 8.4 – 8.7 [44,124]
rotigotine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 8.4 pKi 42
⤷ pKi 8.4 (Ki 4x10-9 M) [42]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 8.3 pKi 103,132
⤷ pKi 8.3 (Ki 5.01x10-9 M) [103,132]
7-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.1 – 8.4 pKi 18,30,44,90,124
⤷ pKi 7.1 – 8.4 (Ki 7.94x10-8 – 3.98x10-9 M) [18,30,44,90,124]
ropinirole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 7.7 pKi 57
⤷ pKi 7.7 (Ki 1.9x10-8 M) [57]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 7.7 pKi 133
⤷ pKi 7.7 [133]
7-trans-OH-PIPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.7 pKi 30
⤷ pKi 7.7 [30]
bromocriptine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 7.1 – 8.2 pKi 44,103,124
⤷ pKi 7.1 – 8.2 [44,103,124]
PD 128907 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.6 – 7.7 pKi 118,124
⤷ pKi 7.6 – 7.7 (Ki 2.51x10-8 – 1.99x10-8 M) [118,124]
quinpirole Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.3 – 7.8 pKi 18,133
⤷ pKi 7.3 – 7.8 [18,133]
quinelorane Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.2 – 7.4 pKi 104,132
⤷ pKi 7.2 – 7.4 [104,132]
quinpirole Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.4 – 8.0 pKi 18,98,104,112,124,132-133,144
⤷ pKi 6.4 – 8.0 (Ki 3.98x10-7 – 1x10-8 M) [18,98,104,112,124,132-133,144]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.1 pKi 133
⤷ pKi 7.1 [133]
dopamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.4 – 7.3 pKi 18,44,124,133
⤷ pKi 6.4 – 7.3 [18,44,124,133]
apomorphine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 6.1 – 7.6 pKi 18,44,103,124,132
⤷ pKi 6.1 – 7.6 [18,44,103,124,132]
compound 3 [PMID: 23134120] Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pKi 136
⤷ pKi 6.8 (Ki 1.68x10-7 M) [136]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.6 pKi 103
⤷ pKi 6.6 [103]
HS665 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pKi 136
⤷ pKi 6.6 (Ki 2.82x10-7 M) [136]
vilazodone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.2 pIC50 58
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [58]
PF-592379 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pIC50 32
⤷ pIC50 6.7 (IC50 2.15x10-7 M) [32]
View species-specific agonist tables
Agonist Comments
PF-592379 has no measurable binding to D1, D2 or D5 receptors [32].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]nemonapride Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 10.3 pKd 91
⤷ pKd 10.3 [91]
[3H]spiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Antagonist 9.9 pKd 60,157
⤷ pKd 9.9 (Kd 1.25x10-10 M) [60,157]
S33084 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 102
⤷ pKi 9.6 (Ki 2.5x10-10 M) [102]
perospirone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.6 pKi 132
⤷ pKi 9.6 (Ki 2.8x10-10 M) [132]
R-VK4-40 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.5 pKi 63
⤷ pKi 9.5 (Ki 2.9x10-10 M) [63]
nafadotride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.5 pKi 125
⤷ pKi 9.5 (Ki 3x10-10 M) [125]
nemonapride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.2 – 9.3 pKi 90,141
⤷ pKi 9.2 – 9.3 [90,141]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.2 pKi 133
⤷ pKi 9.2 [133]
PG01037 Small molecule or natural product Hs Antagonist 9.2 pKi 55
⤷ pKi 9.2 [55]
flupentixol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.0 pKi 44
⤷ pKi 9.0 (Ki 1.1x10-9 M) [44]
eticlopride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.8 pKi 90,141
⤷ pKi 8.8 [90,141]
NGB 2904 Small molecule or natural product Hs Antagonist 8.8 pKi 149
⤷ pKi 8.8 [149]
sertindole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 – 8.8 pKi 6,127,129
⤷ pKi 8.0 – 8.8 (Ki 1x10-8 – 1.6x10-9 M) [6,127,129]
prochlorperazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 9
⤷ pKi 8.4 (Ki 4.45x10-9 M) [9]
chlorprothixene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.3 pKi 145
⤷ pKi 8.3 (Ki 4.56x10-9 M) [145]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 127
⤷ pKi 8.2 (Ki 6.4x10-9 M) [127]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 pKi 92
⤷ pKi 8.1 (Ki 7.99x10-9 M) [92]
haloperidol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.5 – 8.6 pKi 44,130,132,143
⤷ pKi 7.5 – 8.6 [44,130,132,143]
SB 277011-A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.0 pKi 119
⤷ pKi 8.0 (Ki 1x10-8 M) [119]
raclopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 104
⤷ pKi 7.9 [104]
pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 8.6 pKi 44,132
⤷ pKi 7.0 – 8.6 [44,132]
loxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.7 pKi 129
⤷ pKi 7.7 (Ki 2.1x10-8 M) [129]
mesoridazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.6 pKi 29
⤷ pKi 7.6 (Ki 2.3x10-8 M) [29]
raclopride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.5 pKi 133
⤷ pKi 7.5 [133]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 – 7.5 pKi 18
⤷ pKi 7.3 – 7.5 [18]
pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.4 pKi 133
⤷ pKi 7.4 [133]
amisulpride Small molecule or natural product Approved drug Rn Antagonist 7.4 pKi 133
⤷ pKi 7.4 [133]
(+)-S-14297 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 – 7.9 pKi 100,104
⤷ pKi 6.9 – 7.9 (Ki 1.26x10-7 – 1.3x10-8 M) [100,104]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 8.0 pKi 44,118,141
⤷ pKi 6.7 – 8.0 [44,118,141]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.2 – 7.5 pKi 44,132
⤷ pKi 7.2 – 7.5 [44,132]
domperidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.1 – 7.6 pKi 44,132
⤷ pKi 7.1 – 7.6 [44,132]
sulpiride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.8 – 7.8 pKi 18
⤷ pKi 6.8 – 7.8 (Ki 1.42x10-7 – 1.4x10-8 M) [18]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.2 pKi 133
⤷ pKi 7.2 [133]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 – 7.4 pKi 44,133
⤷ pKi 7.0 – 7.4 [44,133]
(-)-sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.7 – 7.7 pKi 44,132,141
⤷ pKi 6.7 – 7.7 (Ki 2.07x10-7 – 2x10-8 M) [44,132,141]
haloperidol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.0 pKi 133
⤷ pKi 7.0 [133]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 pKi 104
⤷ pKi 7.0 [104]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 133
⤷ pKi 7.0 [133]
domperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.0 pKi 133
⤷ pKi 7.0 [133]
promazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.8 pKi 19
⤷ pKi 6.8 (Ki 1.59x10-7 M) [19]
trans-flupenthixol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 pKi 44
⤷ pKi 6.5 (Ki 3x10-7 M) [44]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 133
⤷ pKi 6.4 [133]
(+)-AJ76 Small molecule or natural product Hs Antagonist 5.9 – 6.2 pKi 104,132
⤷ pKi 5.9 – 6.2 [104,132]
(+)-AJ76 Small molecule or natural product Rn Antagonist 6.0 pKi 133
⤷ pKi 6.0 [133]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.2 – 6.3 pKi 44,132
⤷ pKi 5.2 – 6.3 [44,132]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 5.7 pKi 133
⤷ pKi 5.7 [133]
View species-specific antagonist tables
Allosteric Modulators
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Ligand Sp. Action Value Parameter Reference
SB269652 Small molecule or natural product Click here for species-specific activity table Hs Negative ~9.0 pKi 45
⤷ pKi ~9.0 (Ki ~1x10-9 M) [45]
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0002031 G protein-coupled receptor internalization IDA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Potassium channel
References:  27,86,116-117,128
Tissue Distribution Click here for help
Ventral striatum/nucleus accumbens > neostriatum, cerebral cortex, cerebellar cortex.
Species:  Human
Technique:  Autoradiography.
References:  59,76
Brain: nucleus accumbens and islands of Calleja.
Species:  Human
Technique:  in situ hybridization.
References:  78
Brain: mesencephalic dopamine neurons in substantia nigra and ventral tegmental area.
Species:  Rat
Technique:  In situ hybridization.
References:  41
Kidney: proximal tubules
Species:  Rat
Technique:  Immunohistochemistry
References:  108
Brain: Post-synaptic elements of asymmetric synapses of the nucleus accumbens
Species:  Rat
Technique:  Immuno-electron microscopy
References:  87,134
Brain: islands of Cajella, olafactory bulb, pituitary intermediate lobe > nucleus accumbens, molecular layer of the vestibulocerebellum, substantia nigra pars compacta.
Species:  Rat
Technique:  Autoradiography and in situ hybridization.
References:  12,40,48,77,83,89,111,120
Accumbens nucleus, islands of Calleja, bed nucleus of the stria terminalis, hippocampus, mammillary nuclei, substantia nigra.
Species:  Rat
Technique:  in situ hybridization.
References:  14
Expression Datasets Click here for help

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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 Click here for help
Measurement of extracellular acidification in CHO cells transfected with the human D3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Increase in extracellular acidification.
References:  17
Measurement of adenylyl cyclase activity in CHO cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of adenylyl cyclase.
References:  27
Measurement of extracellular acidification rates in CHO cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Increase in extracellular acidification rates.
References:  27
Measurement of extracellular acidification and D3 receptor membrane density in C6 glioma cells transfected with the rat D3 receptor.
Species:  Rat
Tissue:  C6 glioma cells.
Response measured:  Increase in extracellular acidification rate and receptor density.
References:  34
Measurement of c-fos activation and increased mitogenesis in neuroblastoma-glioma hybrid cells (NG108-15) transfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Increase in c-fos activation and mitogenesis.
References:  116
Measurement of cAMP accumulation in cultured Xenopus laevis melanophores transfected with the human D3 receptor.
Species:  Human
Tissue:  Cultured Xenopus laevis melanophores.
Response measured:  Inhibition of cAMP accumulation.
References:  117
Measurement of whole-cell potassium current in NG108-15 cells tranfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Reduction of peak whole-cell potassium current.
References:  86
Measurement of activation of GIRK1 in Xenopus oocytes transfected with the human D3 receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK1.
References:  148
Measurement of mitogenesis in NG108-15 cells transfected with the human D3 receptor.
Species:  Human
Tissue:  NG108-15 cells.
Response measured:  Increase in mitogenesis.
References:  124
Measurement of melanocyte aggregation in Xenopus melanocytes transfected with the human D3 receptor.
Species:  Human
Tissue:  Xenopus melanocytes.
Response measured:  Stimulation of melanocyte aggregation.
References:  17,118
Measurement of activation of an 85 pS K+ channel known to be activated by dopamine and the "D2-like" agonist quinpirole.
Species:  Human
Tissue:  Freshly dissociated rat caudate-putamen neurons.
Response measured:  Activation of K+ channel.
References:  85
Measurement of dopamine release from a mesencephalic clonal cell line transfected with the D3 receptor.
Species:  Human
Tissue:  Neuronal mesencephalic MN9D cells.
Response measured:  Inhibition of dopamine release.
References:  142
Measurement of K+-stimulated tyrosine hydroxylase activity in D3 receptor-expressing MN9D cells.
Species:  Human
Tissue:  MN9D cells
Response measured:  Decrease in K+-stimulated tyrosine hydroxylase activity.
References:  109
Measurement of cAMP levels in HEK 293 cells transfected with the human D3 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  94
Measurement of Cl- currents in Xenopus oocytes transfected with murine D3L and D3S receptors.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of Cl- influx.
References:  131
Measurement of β-arrestin translocation in CHO cells with the human D3 receptor.
Species:  Human
Tissue:  CHO cells
Response measured:  β-arrestin translocation
References:  11,97,151
Physiological Functions Click here for help
Inhibition of dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  37,118
Stimulation of the D3 receptor produces an aversive effect in a conditioned place-preference paradigm.
Species:  Rat
Tissue:  In vivo.
References:  25
Hyperpolarization of neurons and inhibition of cell firing.
Species:  Rat
Tissue:  Substantia nigra pars compacta and ventral tegmental area of rat brain slices.
References:  15
Activation increases cell division.
Species:  Rat
Tissue:  CHO cells.
References:  27
Inhibition of locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  2,36,38,49,65,67,70,84,95,118,125,139-140,146-147
Modulation of motor activity.
Species:  Mouse
Tissue:  In vivo.
References:  137
Stimulation of yawning and hypothermia.
Species:  Rat
Tissue:  In vivo.
References:  2,37,67,73,99-100,104
Modulation of sniffing behaviour.
Species:  Rat
Tissue:  In vivo.
References:  36
Modulation of penile erection and ejaculatory behaviour.
Species:  Rat
Tissue:  In vivo.
References:  21,73
Modulation of self-administration of cocaine.
Species:  Rat
Tissue:  In vivo.
References:  20
Modulation of self-stimulation of the ventral tegmental area.
Species:  Rat
Tissue:  In vivo.
References:  38
Modulation of reinforcing effects of cocaine and d-amphetamine.
Species:  Rat
Tissue:  In vivo.
References:  69
Stimulation of the D3 receptor decreases the rate of food-reinforced responding in a fixed-ratio operant paradigm.
Species:  Rat
Tissue:  In vivo.
References:  123
A D3 agonist with relative selectivity for the dopamine D3 receptor, inhibits the firing of both A9 and A10 dopamine neurons and causes current-dependent inhibitions of spontaneously active or glutamate-driven caudate-putamen and nucleus accumbens neurons.
Species:  Rat
Tissue:  Substantia nigra pars compacta and ventral tegmental area dopamine neurons, and caudate-putamen and nucleus accumbens neurons in vivo.
References:  85
Systemic administration of a D3 receptor agonist decreases extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and dopaminergic neuronal activity in the ventral tegmental area.
Species:  Rat
Tissue:  In vivo.
References:  39
A D3 agonist inhibits substantia nigra pars compacta dopamine single cell firing.
Species:  Rat
Tissue:  In vivo.
References:  72
A D3 agonist inhibits ventral tagmental area dopamine single cell firing.
Species:  Rat
Tissue:  In vivo.
References:  81
Administration of a D3 agonist to freely moving rats decreases dialysate levels of dopamine in the nucleus accumbens.
Species:  Rat
Tissue:  In vivo.
References:  122
Application of a D3 receptor agonist reduces electrically-evoked dopamine release from the nucleus accumbens and striatum.
Species:  Rat
Tissue:  Nucleus accumbens and striatal slices.
References:  154
Modulation of dopamine synthesis.
Species:  Rat
Tissue:  In vivo.
References:  5,46,53,118
Blockade of the D3 receptor inhibits dizocilpine (MK-801)-induced hyperactivity.
Species:  Mouse
Tissue:  In vivo.
References:  82
Blockade of the D3 receptor disrupts drug-associated cue-induced craving and stress-induced craving.
Species:  Rat
Tissue:  In vivo.
References:  4,24,47,50,113,115,150
Blockade of the D3 receptor enhances monoaminergic and cholinergic neurotransmission.
Species:  Rat
Tissue:  In vivo.
References:  74-75,101-102
Application of a D3 receptor agonist reduces electrically-evoked dopamine release from the nucleus accumbens and striatum.
Species:  Rat
Tissue:  Nucleus accumbens and striatal slices.
References:  154
Modulation by the D3 receptor of drug-induced place preference.
Species:  Rat
Tissue:  In vivo.
References:  7,10,23,56,61
Reciprocal regulation of D3 receptor and NMDA receptor through Ca2+/calmodulin-dependent protein kinase II
Species:  Rat
Tissue:  GST-constructs and nucleus accumbens extracts.
References:  87
Selective D3 antagonists induced positive cerebral blood volume (CBV) changes whereas D3 agonism using 7-OH-DPAT induced negative CBV changes.
Species:  Rat
Tissue:  Nucleus accumbens, antero-medial striatum, cingulate cortex, thalamus, interpeduncular region and hypothalamus.
References:  28
Regulation of renal function and blood pressure by D3 receptors.
Species:  Rat
Tissue:  In vivo.
References:  88,155-156
Physiological Consequences of Altering Gene Expression Click here for help
D3 receptor knockout mice exhibit altered circadian pattern in spinal dopamine synthesis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  31
D3 receptor knockout mice exhibit higher basal levels of extracellular dopamine compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  33,64
D3 receptor knockout mice display enhanced hyperactivity when compared to the wild-type, although these effects may be limited.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1,13,153
D3 receptor knockout mice display a transient increase in activity in a novel environment compared with wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  71,152
D3 receptor knockout mice exhibit increased behavioural sensitivity to combined injections of D1 and D2 class receptor agonists, cocaine and amphetamine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  153
D3 receptor knockout mice exhibit reduced anxiety.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  138
D3 receptor knockout mice exhibit renin-dependent hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
D3 receptor knockout mice exhibit increased gene expression in striatal neurons following acute administration of cocaine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  22
D3 receptor knockout mice exhibit aggravation of the development of physical dependence on ethanol.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  107
D3 receptor knockout mice exhibit increased morphine-induced rewarding effects and potentiation of morphine-induced hyperlocomotion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  106
D3 receptor knockout mice display similar effects (reward/intake) of ethanol as wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
D3 receptor knockout mice exhibit increased D1/D2 receptor-mediated intracellular signalling.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  105
D3 receptor knockout mice exhibit increased adiposity induced by a high-fat diet.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  96
D3 receptor knockout mice exhibit neuroadaptive changes which support the role of D3 receptors as autoreceptors.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  80
D3 receptor knockout mice display increased susceptibility to cocaine addition
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  135
Dopamine is more efficacious at the D3 receptor Gly9 compared to Ser9 variant.
Species:  Human
Tissue:  HEK293 cells
Technique:  Binding, adenylate cyclase inhibition, MAPK phosphorylation
References:  62
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
+|Cm|Drd3tm1Stl Cm/+,Drd3tm1Stl/Drd3tm1Stl
involves: 101/H * 129S2/SvPas * C3H/HeH * C3H/HeSn * C57BL/6J		 MGI:88424  MGI:94925  MP:0009748 abnormal behavioral response to addictive substance PMID: 19840852 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001454 abnormal cued conditioning behavior PMID: 9354330 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001905 abnormal dopamine level PMID: 10391470 
Drd2tm1Schm|Drd3+|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001905 abnormal dopamine level PMID: 10391470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005449 abnormal food intake PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0006001 abnormal intestinal transit time PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0006003 abnormal large intestinal transit time PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2tm1Schm|Drd3+|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2+|Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2+,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001392 abnormal locomotor activity PMID: 10391470 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0001666 abnormal nutrient absorption PMID: 16525059 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0000676 abnormal water content PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001262 decreased body weight PMID: 10391470 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0001262 decreased body weight PMID: 16525059 
Drd3tm1Rmw Drd3tm1Rmw/Drd3tm1Rmw
involves: 129P2/OlaHsd		 MGI:94925  MP:0005643 decreased dopamine level PMID: 12044470 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001442 decreased grooming behavior PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001442 decreased grooming behavior PMID: 8700864 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0001505 hunched posture PMID: 10391470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 9354330 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001399 hyperactivity PMID: 8700864 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005669 increased circulating leptin level PMID: 15084447 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003867 increased defecation PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003911 increased drinking behavior PMID: 16525059 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
B6.Cg-Drd2 Drd3		 MGI:94924  MGI:94925  MP:0003909 increased eating behavior PMID: 16525059 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 9354330 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0001415 increased exploration in new environment PMID: 8700864 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005458 increased percent body fat PMID: 15084447 
Drd3tm1Rmw Drd3tm1Rmw/Drd3tm1Rmw
involves: 129P2/OlaHsd		 MGI:94925  MP:0001409 increased stereotypic behavior PMID: 12044470 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0005455 increased susceptibility to weight gain PMID: 15084447 
Drd3tm1Stl Drd3tm1Stl/Drd3tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:94925  MP:0010024 increased total body fat amount PMID: 15084447 
Drd3tm1Dac Drd3tm1Dac/Drd3tm1Dac
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0002574 increased vertical activity PMID: 8700864 
Drd3+|Drd3tm1Dac Drd3tm1Dac/Drd3+
involves: 129S4/SvJae * C57BL/6		 MGI:94925  MP:0002574 increased vertical activity PMID: 8700864 
Drd2tm1Schm|Drd3tm1Schm Drd2tm1Schm/Drd2tm1Schm,Drd3tm1Schm/Drd3tm1Schm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:94924  MGI:94925  MP:0002082 postnatal lethality PMID: 10391470 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Major affective disorder 1; MAFD1
Synonyms: Bipolar affective disorder
Manic depressive-psychosis
OMIM: 125480
Role:  The Ba1I polymorphism has been associated with bipolar disorder
References:  110
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Role:  The Ba1I restriction fragment length polymorphism (corresponding to a point mutation in the 1st exon and resulting in a serine-to-glycine substitution in the N-terminal extracellular domain of the receptor) has been associated with schizophrenia.
References:  35,66,93
Disease:  Tremor, hereditary essential, 1; ETM1
Synonyms: Essential tremor [Disease Ontology: DOID:4990]
Hereditary essential tremor [Orphanet: ORPHA862]
Disease Ontology: DOID:4990
OMIM: 190300
Orphanet: ORPHA862
Comments:  Gly9 variant confers disease risk
References:  62
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human S9G Gain of function mutation. Functional variant of the dopamine D3 receptor which is associated with risk and age-at-onset of essential tremor 62
General Comments
Alternative splicing leads to a 425aa isoform in mouse [43] and several shorter presumably inactive isoforms in rat [52] and human [126]. Two polymorphic variants [Ser9] and [Gly9] in human [79]. The organization of the coding sequence of the human gene has been established [54]. Anti-psychotic drugs display closely similar or slightly lower antagonist affinity at D3 compared to D2 receptors. S(+)14297, initially reported as a D3 receptor antagonist [104] displays full agonist activity in two functional assays [114].

References

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