Dopamine receptor D3
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DRD3
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| Location (UCSC) | Chr 3: 114.13 – 114.2 Mb | Chr 16: 43.57 – 43.64 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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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
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
- trans-N-{4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide, full agonist, > 200-fold binding selectivity over D4, D2, 5-HT1A, and α1-receptors[19]
- (-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol[20]
- 5-OH-DPAT
- 7-OH-DPAT
- Pergolide[21]
- 8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole)
- Apomorphine (non-selective dopamine agonist)
- Bromocriptine (non-selective dopamine agonist)
- Captodiame
- CJ-1639[22]
- compound R,R-16: 250x binding selectivity over D2[23]
- Dopamine (endogenous agonist)
- ES609
- FAUC 54
- FAUC 73
- PD-128,907
- PF-219,061 (extremely selective) [24]
- PF-592,379[25]
- Piribedil[26] (non-selective dopamine agonist)
- Pramipexole (non-selective dopamine agonist)
- Quinelorane (also D2 agonist)
- Quinpirole (also D2 agonist)
- Ropinirole (non-selective dopamine agonist)
- Rotigotine (non-selective dopamine agonist)
Partial agonists
- Aripiprazole (non-selective)
- BP-897[27]
- Brexpiprazole (non-selective)
- Buspirone (non-selective)
- Cariprazine
- CJB 090
- CJ-1037 (extremely selective) [28]
- FAUC 460 (highly selective) [29]
- FAUC 346 (highly selective)[30]
- Pardoprunox (non-selective)
- Roxindole (possibly a partial agonist at the D3 autoreceptors, non-selective)
- OS-3-106
- UH-232
- WW-III-55
Antagonists
- 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
Dopamine receptor D3 has been shown to
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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000151577 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022705 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 28411786.
- ^ a b "Entrez Gene: DRD3 dopamine receptor D3".
- PMID 17174156.
- PMID 35469394.
- PMID 31765822.
- PMID 19549514.
- PMID 16959244.
- S2CID 211831700.
- PMID 35463692.
- PMID 35965941.
- PMID 19020413.
- PMID 20385162.
- PMID 22227455.
- PMID 19426754.
- S2CID 42910160.
- PMID 18072730.
- PMID 10082211.
- PMID 22125662.
- PMID 19324548.
- PMID 17976986.
- PMID 22470105.
- PMID 8905329.
- PMID 17985117.
- PMID 18785726.
- PMID 18834111.
- ^ PMID 12361386.
- ^ {{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 }}
- PMID 20228156.
- PMID 19331412.
- PMID 17627675.
- PMID 14499480.
- S2CID 19901660.
- PMID 27325396.
- PMID 31143436.
- PMID 29361389.
- PMID 30363458.
Further reading
- Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January 1998). "Dopamine receptors: from structure to function". Physiological Reviews. 78 (1): 189–225. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
- "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.