Wikipedia

Dopamine receptor D3

(Redirected from D3 receptor)

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

DRD3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDRD3, D3DR, ETM1, FET1, dopamine receptor D3
External IDsOMIM: 126451; MGI: 94925; HomoloGene: 623; GeneCards: DRD3; OMA:DRD3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1814

13490

Ensembl

ENSG00000151577

ENSMUSG00000022705

UniProt

P35462

P30728

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

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

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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

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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

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Agonists

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Partial agonists

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Antagonists

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Allosteric modulators

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Interactions

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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

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151577 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022705 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, et al. (September 1991). "Chromosomal localization of the human D3 dopamine receptor gene". Human Genetics. 87 (5): 618–620. doi:10.1007/bf00209024. PMID 1916765. S2CID 28411786.
  6. ^ a b "Entrez Gene: DRD3 dopamine receptor D3".
  7. ^ Joyce JN, Millan MJ (February 2007). "Dopamine D3 receptor agonists for protection and repair in Parkinson's disease". Current Opinion in Pharmacology. 7 (1): 100–105. doi:10.1016/j.coph.2006.11.004. PMID 17174156.
  8. ^ Favier M, Carcenac C, Savasta M, Carnicella S (2022). "Dopamine D3 Receptors: A Potential Target to Treat Motivational Deficits in Parkinson's Disease". Current Topics in Behavioral Neurosciences. Vol. 60. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 109–132. doi:10.1007/7854_2022_316. ISBN 978-3-031-23057-8. PMID 35469394.
  9. ^ Yang P, Perlmutter JS, Benzinger TL, Morris JC, Xu J (January 2020). "Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?". Ageing Research Reviews. 57: 100994. doi:10.1016/j.arr.2019.100994. PMC 6939386. PMID 31765822.
  10. ^ Breuer ME, Groenink L, Oosting RS, Buerger E, Korte M, Ferger B, Olivier B (August 2009). "Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats". European Journal of Pharmacology. 616 (1–3): 134–140. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514.
  11. ^ Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). "Antidepressant properties of rotigotine in experimental models of depression". European Journal of Pharmacology. 548 (1–3): 106–114. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244.
  12. ^ Oliveira V, Videira G, Mendes A (July 2020). "Loss of Awareness after Continuous Apomorphine Infusion Withdrawal in Parkinson's Disease". The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques. 47 (4): 576–577. doi:10.1017/cjn.2020.43. hdl:10400.16/2536. PMID 32122433. S2CID 211831700.
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  16. ^ Chang WL, Swerdlow NR, Breier MR, Thangaraj N, Weber M (June 2010). "Parametric approaches towards understanding the effects of the preferential D3 receptor agonist pramipexole on prepulse inhibition in rats". Pharmacology, Biochemistry, and Behavior. 95 (4): 473–478. doi:10.1016/j.pbb.2010.04.001. PMC 2889248. PMID 20385162.
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  20. ^ Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E, et al. (January 2008). "Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action". Journal of Medicinal Chemistry. 51 (1): 101–117. doi:10.1021/jm070860r. PMID 18072730.
  21. ^ Perachon S, Schwartz JC, Sokoloff P (February 1999). "Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors". European Journal of Pharmacology. 366 (2–3): 293–300. doi:10.1016/S0014-2999(98)00896-6. PMID 10082211.
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  24. ^ Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL, et al. (December 2007). "Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route". Bioorganic & Medicinal Chemistry Letters. 17 (24): 6691–6696. doi:10.1016/j.bmcl.2007.10.059. PMID 17976986.
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  26. ^ Cagnotto A, Parotti L, Mennini T (October 1996). "In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study". European Journal of Pharmacology. 313 (1–2): 63–67. doi:10.1016/0014-2999(96)00503-1. PMID 8905329.
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Further reading

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