Dopamine receptor D3

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DRD3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDRD3, D3DR, ETM1, FET1, dopamine receptor D3
External IDsOMIM: 126451 MGI: 94925 HomoloGene: 623 GeneCards: DRD3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_007877

RefSeq (protein)

NP_000787
NP_001269492
NP_001277738
NP_387512

NP_031903

Location (UCSC)Chr 3: 114.13 – 114.2 MbChr 16: 43.57 – 43.64 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.[5][6]

This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions.[citation needed] It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease.[7] Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD).[6]

Function

Alpha-synuclein (α-Syn) aggregation via Lewy bodies inclusion, a pathogenic signature exclusively present in PD patients, is decreased by D3 agonists while DA content is elevated by inhibiting DA reuptake and breakdown. The regulation of α-Syn aggregation and clearance enhances brain-derived neurotrophic factor (BDNF) secretion, which ultimately ameliorates neuroinflammation and oxidative stress while promoting neurogenesis and interacting with other DA receptors.[8][9]

D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.[10][11] Apomorphine has the ability to help PD patients with their cognition awareness.[12] In addition to having antidepressant properties such as regulating the depression-like behaviors and depression development, pramipexole has the capability to prevent and slow down cell apoptosis as well as to restore damaged neural networks and connections while rotigotine help PD patients to attenuates hyperpyrexia syndrome and schizophrenia.[13][14]

Animal studies

D3 agonists have been shown to disrupt prepulse inhibition of startle (PPI), a cross-species measure that recapitulates deficits in sensorimotor gating in neuropsychiatric disorders such as schizophrenia.[15][16][17] In contrast, D3-preferring antagonists have antipsychotic-like profiles in measures of PPI in rats.[18]

Ligands

Agonists

Partial agonists

Antagonists

Interactions

Dopamine receptor D3 has been shown to interact with CLIC6[35] and EPB41L1.[36]

DRD3 Ser9Gly polymorphism(rs6280), which is a single nucleotide polymorphism (SNP) with variant base C/T is linked to variation in PD such as depression severity, impulse control disorders, behavioral addiction and aberrant decision-making.[37][38][39][40]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151577 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022705 - Ensembl, May 2017
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  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.