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Dopamine receptor D3

Summary

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
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 edit

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 edit

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 edit

Agonists edit

Partial agonists edit

Antagonists edit

  • Most Antipsychotics
  • Amisulpride (non-selective)
  • Buspirone
  • Cyproheptadine (non-selective)
  • PG 01037 [31][32]
  • Domperidone (peripheral D2 and D3 antagonist)
  • FAUC 365, silent antagonist, subtype selective[30]
  • GR-103,691
  • GSK598809 (highly selective)
  • Haloperidol (non-selective, blocks all dopamine receptor subtypes, though D3 with the strongest affinity)
  • N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides[33]
  • Nafadotride
  • NGB-2904[34]
  • PNU-99,194 (moderately selective over D2)
  • Raclopride (also D2 antagonist)
  • S-14,297 (selective)
  • S33084
  • SB-277011-A, selective D3 antagonist, 80x selectivity over D2 with no partial agonist effects, used in drug addiction research as a potential therapy for addiction to several different drugs
  • SR 21502 (highly selective)
  • Sulpiride (also D2 antagonist)
  • U99194
  • YQA14 (high affinity and selectivity)
  • Risperidone

Interactions edit

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 edit

References edit

  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.
  13. ^ Sun Y, Cui B, Ye L, Hu Y, Pan Y (2022). "Pramipexole Inhibits Neuronal Apoptosis in Rats with Parkinson's Disease". Journal of Healthcare Engineering. 2022: 7002630. doi:10.1155/2022/7002630. PMC 9020956. PMID 35463692.
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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.
  17. ^ Chang WL, Weber M, Breier MR, Saint Marie RL, Hines SR, Swerdlow NR (February 2012). "Stereochemical and neuroanatomical selectivity of pramipexole effects on sensorimotor gating in rats". Brain Research. 1437: 69–76. doi:10.1016/j.brainres.2011.12.007. PMC 3268831. PMID 22227455.
  18. ^ Weber M, Chang WL, Durbin JP, Park PE, Luedtke RR, Mach RH, Swerdlow NR (August 2009). "Using prepulse inhibition to detect functional D3 receptor antagonism: effects of WC10 and WC44". Pharmacology, Biochemistry, and Behavior. 93 (2): 141–147. doi:10.1016/j.pbb.2009.04.022. PMC 2720754. PMID 19426754.
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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.
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  22. ^ Chen J, Collins GT, Levant B, Woods J, Deschamps JR, Wang S (August 2011). "CJ-1639: A Potent and Highly Selective Dopamine D3 Receptor Full Agonist". ACS Medicinal Chemistry Letters. 2 (8): 620–625. doi:10.1021/ml200100t. PMC 3224040. PMID 22125662.
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  25. ^ Collins GT, Butler P, Wayman C, Ratcliffe S, Gupta P, Oberhofer G, Caine SB (June 2012). "Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats". Behavioural Pharmacology. 23 (3): 280–291. doi:10.1097/FBP.0b013e3283536d21. PMC 3365486. PMID 22470105.
  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.
  27. ^ Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby CR, Heidbreder C, et al. (March 2008). "The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats". Psychopharmacology. 196 (4): 533–542. doi:10.1007/s00213-007-0986-6. PMC 3713235. PMID 17985117.
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  30. ^ a b Bettinetti L, Schlotter K, Hübner H, Gmeiner P (October 2002). "Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists". Journal of Medicinal Chemistry. 45 (21): 4594–4597. doi:10.1021/jm025558r. PMID 12361386.
  31. ^ {{cite journal | vauthors = Grundt P, Carlson EE, Cao J, Bennett CJ, McElveen E, Taylor M, Luedtke RR, Newman AH | display-authors = 6 | title = Novel heterocyclic trans olefin analogues of N-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as selective probes with high affinity for the dopamine D3 receptor | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 3 | pages = 839–848 | date = February 2005 | pmid = 15689168 | doi = 10.1021/jm049465g }}
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Further reading edit

  • Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January 1998). "Dopamine receptors: from structure to function". Physiological Reviews. 78 (1): 189–225. doi:10.1152/physrev.1998.78.1.189. PMID 9457173.
  • Sidhu A, Niznik HB (November 2000). "Coupling of dopamine receptor subtypes to multiple and diverse G proteins". International Journal of Developmental Neuroscience. 18 (7): 669–677. doi:10.1016/S0736-5748(00)00033-2. PMID 10978845. S2CID 21002590.
  • Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (September 1990). "Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics". Nature. 347 (6289): 146–151. Bibcode:1990Natur.347..146S. doi:10.1038/347146a0. PMID 1975644. S2CID 4284114.
  • Giros B, Martres MP, Sokoloff P, Schwartz JC (1991). "[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]". Comptes Rendus de l'Académie des Sciences, Série III. 311 (13): 501–508. PMID 2129115.
  • Liu K, Bergson C, Levenson R, Schmauss C (November 1994). "On the origin of mRNA encoding the truncated dopamine D3-type receptor D3nf and detection of D3nf-like immunoreactivity in human brain". The Journal of Biological Chemistry. 269 (46): 29220–29226. doi:10.1016/S0021-9258(19)62033-8. PMID 7961889.
  • Schmauss C, Haroutunian V, Davis KL, Davidson M (October 1993). "Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia". Proceedings of the National Academy of Sciences of the United States of America. 90 (19): 8942–8946. Bibcode:1993PNAS...90.8942S. doi:10.1073/pnas.90.19.8942. PMC 47477. PMID 8415635.
  • Griffon N, Crocq MA, Pilon C, Martres MP, Mayerova A, Uyanik G, et al. (February 1996). "Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia". American Journal of Medical Genetics. 67 (1): 63–70. doi:10.1002/(SICI)1096-8628(19960216)67:1<63::AID-AJMG11>3.0.CO;2-N. PMID 8678117.
  • Staley JK, Mash DC (October 1996). "Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities". The Journal of Neuroscience. 16 (19): 6100–6106. doi:10.1523/JNEUROSCI.16-19-06100.1996. PMC 6579196. PMID 8815892.
  • Chen CH, Liu MY, Wei FC, Koong FJ, Hwu HG, Hsiao KJ (February 1997). "Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia". American Journal of Medical Genetics. 74 (1): 40–43. doi:10.1002/(SICI)1096-8628(19970221)74:1<40::AID-AJMG9>3.0.CO;2-Z. PMID 9034004.
  • Gulcher JR, Jónsson P, Kong A, Kristjánsson K, Frigge ML, Kárason A, et al. (September 1997). "Mapping of a familial essential tremor gene, FET1, to chromosome 3q13". Nature Genetics. 17 (1): 84–87. doi:10.1038/ng0997-84. PMID 9288103. S2CID 1506516.
  • Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, et al. (November 1998). "SH3 binding domains in the dopamine D4 receptor" (PDF). Biochemistry. 37 (45): 15726–15736. doi:10.1021/bi981634+. PMID 9843378.
  • Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, et al. (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics. 22 (3): 231–238. doi:10.1038/10290. PMID 10391209. S2CID 195213008.
  • Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth CG, et al. (July 1999). "Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist". Nature. 400 (6742): 371–375. Bibcode:1999Natur.400..371P. doi:10.1038/22560. PMID 10432116. S2CID 4351316.
  • Ilani T, Ben-Shachar D, Strous RD, Mazor M, Sheinkman A, Kotler M, Fuchs S (January 2001). "A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 98 (2): 625–628. doi:10.1073/pnas.021535398. PMC 14638. PMID 11149951.
  • Lin R, Karpa K, Kabbani N, Goldman-Rakic P, Levenson R (April 2001). "Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A". Proceedings of the National Academy of Sciences of the United States of America. 98 (9): 5258–5263. Bibcode:2001PNAS...98.5258L. doi:10.1073/pnas.011538198. PMC 33197. PMID 11320256.
  • Oldenhof J, Ray A, Vickery R, Van Tol HH (June 2001). "SH3 ligands in the dopamine D3 receptor". Cellular Signalling. 13 (6): 411–416. doi:10.1016/S0898-6568(01)00157-7. PMID 11384839.
  • Soma M, Nakayama K, Rahmutula D, Uwabo J, Sato M, Kunimoto M, et al. (January 2002). "Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese". Medical Science Monitor. 8 (1): CR1–CR4. PMID 11796958.

External links edit

  • "Dopamine Receptors: D3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • Receptors,+Dopamine+D3 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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

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