Dopamine receptor D3

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Dopamine receptor D3
3PBL (D3).png
Dopamine D3 receptor with Eticlopride(PDB 3PBL)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DRD3 ; D3DR; ETM1; FET1
External IDs OMIM126451 MGI94925 HomoloGene623 IUPHAR: D3 ChEMBL: 234 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 P30728
RefSeq (mRNA) NM_000796 NM_007877
RefSeq (protein) NP_000787 NP_031903
Location (UCSC) Chr 3:
113.85 – 113.92 Mb
Chr 16:
43.76 – 43.82 Mb
PubMed search [1] [2]

D3 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.[3] 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]

D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.[4][5]

Ligands[edit]

Agonists[edit]

Partial agonists[edit]

Antagonists[edit]

Interactions[edit]

Dopamine receptor D3 has been shown to interact with CLIC6[21] and EPB41L1.[22]

See also[edit]

References[edit]

  1. ^ Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C et al. (Oct 1991). "Chromosomal localization of the human D3 dopamine receptor gene". Hum Genet 87 (5): 618–20. doi:10.1007/bf00209024. PMID 1916765. 
  2. ^ a b "Entrez Gene: DRD3 dopamine receptor D3". 
  3. ^ Joyce JN, Millan MJ (February 2007). "Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.". Current Opinion in Pharmacology 7 (1): 100–5. doi:10.1016/j.coph.2006.11.004. PMID 17174156. 
  4. ^ Breuer ME, Groenink L, Oosting RS, Buerger E, Korte M, Ferger B et al. (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): 134–40. doi:10.1016/j.ejphar.2009.06.029. PMID 19549514. 
  5. ^ 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): 106–14. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244. 
  6. ^ 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. 
  7. ^ Biswas S, Zhang S, Fernandez F, Ghosh B, Zhen J, Kuzhikandathil E et al. (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. 
  8. ^ 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 Med Chem Lett 2 (8): 620–625. doi:10.1021/ml200100t. PMID 22125662. 
  9. ^ Peglion JL, Poitevin C, Mannoury La Cour C, 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. 
  10. ^ Blagg J, Allerton CM, Batchelor DV, Baxter AD, Burring DJ, Carr CL et al. (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. 
  11. ^ Collins GT, Butler P, Wayman C, Ratcliffe S, Gupta P, Oberhofer G et al. (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. 
  12. ^ 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. doi:10.1016/0014-2999(96)00503-1. PMID 8905329. 
  13. ^ 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): 533–42. doi:10.1007/s00213-007-0986-6. PMID 17985117. 
  14. ^ Chen J, Collins GT, Zhang J, Yang CY, Levant B, Woods 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. PMC 2662387. PMID 18785726. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ Grundt P, Carlson EE, Cao J, Bennett CJ, McElveen E, Taylor M 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. 
  18. ^ Mason CW, Hassan HE, Kim KP, Cao J, Eddington ND, Newman AH et al. (12 March 2010). "Characterization of the Transport, Metabolism, and Pharmacokinetics of the Dopamine D3 Receptor-Selective Fluorenyl- and 2-Pyridylphenyl Amides Developed for Treatment of Psychostimulant Abuse". Journal of Pharmacology and Experimental Therapeutics 333 (3): 854–864. doi:10.1124/jpet.109.165084. PMID 20228156. 
  19. ^ Newman AH, Grundt P, Cyriac G, Deschamps JR, Taylor M, Kumar R 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 (8): 2559–70. doi:10.1021/jm900095y. PMC 2760932. PMID 19331412. 
  20. ^ 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. 
  21. ^ Griffon N, Jeanneteau F, Prieur F, Diaz J, Sokoloff P (2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. Mol. Brain Res. 117 (1): 47–57. doi:10.1016/S0169-328X(03)00283-3. PMID 14499480. 
  22. ^ Binda AV, Kabbani N, Lin R, Levenson R (2002). "D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N". Mol. Pharmacol. 62 (3): 507–13. doi:10.1124/mol.62.3.507. PMID 12181426. 

Further reading[edit]

External links[edit]

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