Dopamine receptor D3: Wikis

  

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Dopamine receptor D3
Identifiers
Symbols DRD3; D3DR; ETM1; FET1; MGC149204; MGC149205
External IDs OMIM126451 MGI94925 HomoloGene623 IUPHAR: D3 GeneCards: DRD3 Gene
RNA expression pattern
PBB GE DRD3 211625 s at tn.png
PBB GE DRD3 214559 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1814 13490
Ensembl ENSG00000151577 ENSMUSG00000022705
UniProt P35462 Q0VEC4
RefSeq (mRNA) NM_000796 NM_007877
RefSeq (protein) NP_000787 NP_031903
Location (UCSC) Chr 3:
115.33 - 115.38 Mb
Chr 16:
43.68 - 43.74 Mb
PubMed search [1] [2]

D(3) dopamine receptor is a protein that in humans is encoded by the DRD3 gene.[1][2]

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. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease. 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).[2]

Contents

Ligands

Numerous non-selective prescription drugs bind to the D3 receptor, notably including some of the newer dopamine agonists used for Parkinson's disease such as pramipexole and ropinirole, but these also bind to D2 and lack the strong receptor type and subtype selectivity that some of the following research compounds afford:

Agonists

  • 8-OH-PBZI (cis-8-Hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1H-benz[e]indole)
  • PF-219,061 ((R)-3-(4-Propylmorpholin-2-yl)phenol): >1000-fold functional (efficiacy) selectivity over D2[3]
  • compound R,R-16: 250x binding selectivity over D2[4]
  • 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[5]
  • (-)-7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol[6]
  • BP-897: partial agonist [7]
  • FAUC 73
  • FAUC 460: partial agonist, outstanding affinity and selectivity[8]
  • FAUC 346: partial agonist, subtype selective[9]
  • PD-128,907
  • compound 12: partial agonist, Ki = 0.41nM, 800x binding selectivity over D2[10]
  • piribedil[11]

Antagonists

  • [12]
  • FAUC 365, silent antagonist, subtype selective[9]
  • compound 29 [13]
  • Nafadotride
  • NGB-2904[14]
  • 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
Chemical structures of selective D3 receptor ligands.


Interactions

Dopamine receptor D3 has been shown to interact with CLIC6[15] and EPB41L1.[16]

See also

References

  1. ^ Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (Oct 1991). "Chromosomal localization of the human D3 dopamine receptor gene". Hum Genet 87 (5): 618–20. PMID 1916765.  
  2. ^ a b "Entrez Gene: DRD3 dopamine receptor D3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1814.  
  3. ^ Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL, Cook AS, Nichols CL, Phipps J, Sanderson VG, Verrier H, Wong S (2007). "Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route". Bioorg. Med. Chem. Lett. 17 (24): 6691–6. doi:10.1016/j.bmcl.2007.10.059. PMID 17976986.  
  4. ^ Peglion JL, Poitevin C, La Cour CM, Dupuis D, Millan MJ (2009). "Modulations of the amide function of the preferential dopamine D3 agonist (R,R)-S32504: Improvements of affinity and selectivity for D3 versus D2 receptors". Bioorg. Med. Chem. Lett. 19 (8): 2133–8. doi:10.1016/j.bmcl.2009.03.015. PMID 19324548.  
  5. ^ Leopoldo M, Lacivita E, Colabufo NA, Berardi F, Perrone R (2006). "Synthesis and binding profile of constrained analogues of N-[4-(4-arylpiperazin-1-yl)butyl]-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands". J. Pharm. Pharmacol. 58 (2): 209–18. doi:10.1211/jpp.58.2.0008. PMID 16451749.  
  6. ^ Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E, Reith ME, Dutta AK (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". J. Med. Chem. 51 (1): 101–17. doi:10.1021/jm070860r. PMID 18072730.  
  7. ^ Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby CR, Heidbreder C, Gaál J, Gardner EL (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): 533–42. doi:10.1007/s00213-007-0986-6. PMID 17985117.  
  8. ^ Dörfler M, Tschammer N, Hamperl K, Hübner H, Gmeiner P (2008). "Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies". J. Med. Chem. 51 (21): 6829–38. doi:10.1021/jm800895v. PMID 18834111.  
  9. ^ a b Bettinetti L, Schlotter K, Hübner H, Gmeiner P (2002). "Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists". J. Med. Chem. 45 (21): 4594–7. doi:10.1021/jm025558r. PMID 12361386.  
  10. ^ Chen J, Collins GT, Zhang J, et al (2008). "Design, synthesis, and evaluation of potent and selective ligands for the dopamine 3 (D3) receptor with a novel in vivo behavioral profile". J. Med. Chem. 51 (19): 5905–8. doi:10.1021/jm800471h. PMID 18785726.  
  11. ^ Cagnotto A, Parotti L, Mennini T (October 1996). "In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study". Eur. J. Pharmacol. 313 (1-2): 63–7. PMID 8905329.  
  12. ^ Newman AH, Grundt P, Cyriac G, et al (2009). "N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists ( parallel) ( perpendicular)". J. Med. Chem. 52: 2559. doi:10.1021/jm900095y. PMID 19331412.  
  13. ^ Grundt P, Carlson EE, Cao J, et al (2005). "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". J. Med. Chem. 48 (3): 839–48. doi:10.1021/jm049465g. PMID 15689168.  
  14. ^ Xi ZX, Gardner EL (2007). "Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction". CNS Drug Reviews 13 (2): 240–59. doi:10.1111/j.1527-3458.2007.00013.x. PMID 17627675.  
  15. ^ Griffon, Nathalie; Jeanneteau Freddy, Prieur Fanny, Diaz Jorge, Sokoloff Pierre (Sep. 2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. Mol. Brain Res. (Netherlands) 117 (1): 47–57. ISSN 0169-328X. PMID 14499480.  
  16. ^ Binda, Alicia V; Kabbani Nadine, Lin Ridwan, Levenson Robert (Sep. 2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. (United States) 62 (3): 507–13. ISSN 0026-895X. PMID 12181426.  

Further reading

  • Missale C, Nash SR, Robinson SW, et al. (1998). "Dopamine receptors: from structure to function.". Physiol. Rev. 78 (1): 189–225. PMID 9457173.  
  • Sidhu A, Niznik HB (2000). "Coupling of dopamine receptor subtypes to multiple and diverse G proteins.". Int. J. Dev. Neurosci. 18 (7): 669–77. doi:10.1016/S0736-5748(00)00033-2. PMID 10978845.  
  • Sokoloff P, Giros B, Martres MP, et al. (1990). "Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.". Nature 347 (6289): 146–51. doi:10.1038/347146a0. PMID 1975644.  
  • Giros B, Martres MP, Sokoloff P, Schwartz JC (1991). "[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]". C. R. Acad. Sci. III, Sci. Vie 311 (13): 501–8. PMID 2129115.  
  • Liu K, Bergson C, Levenson R, Schmauss C (1994). "On the origin of mRNA encoding the truncated dopamine D3-type receptor D3nf and detection of D3nf-like immunoreactivity in human brain.". J. Biol. Chem. 269 (46): 29220–6. PMID 7961889.  
  • Schmauss C, Haroutunian V, Davis KL, Davidson M (1993). "Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia.". Proc. Natl. Acad. Sci. U.S.A. 90 (19): 8942–6. doi:10.1073/pnas.90.19.8942. PMID 8415635.  
  • Griffon N, Crocq MA, Pilon C, et al. (1996). "Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.". Am. J. Med. Genet. 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 (1996). "Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities.". J. Neurosci. 16 (19): 6100–6. PMID 8815892.  
  • Chen CH, Liu MY, Wei FC, et al. (1997). "Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia.". Am. J. Med. Genet. 74 (1): 40–3. 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, et al. (1997). "Mapping of a familial essential tremor gene, FET1, to chromosome 3q13.". Nat. Genet. 17 (1): 84–7. doi:10.1038/ng0997-84. PMID 9288103.  
  • Oldenhof J, Vickery R, Anafi M, et al. (1998). "SH3 binding domains in the dopamine D4 receptor.". Biochemistry 37 (45): 15726–36. doi:10.1021/bi981634. PMID 9843378.  
  • Cargill M, Altshuler D, Ireland J, et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes.". Nat. Genet. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209.  
  • Pilla M, Perachon S, Sautel F, et al. (1999). "Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist.". Nature 400 (6742): 371–5. doi:10.1038/22560. PMID 10432116.  
  • Ilani T, Ben-Shachar D, Strous RD, et al. (2001). "A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes.". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 625–8. doi:10.1073/pnas.021535398. PMID 11149951.  
  • Lin R, Karpa K, Kabbani N, et al. (2001). "Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A.". Proc. Natl. Acad. Sci. U.S.A. 98 (9): 5258–63. doi:10.1073/pnas.011538198. PMID 11320256.  
  • Oldenhof J, Ray A, Vickery R, Van Tol HH (2001). "SH3 ligands in the dopamine D3 receptor.". Cell. Signal. 13 (6): 411–6. doi:10.1016/S0898-6568(01)00157-7. PMID 11384839.  
  • Soma M, Nakayama K, Rahmutula D, et al. (2002). "Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese.". Med. Sci. Monit. 8 (1): CR1–4. PMID 11796958.  

External links

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








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