D3 dopaminski receptor je protein koji je kod ljudi kodiran DRD3 genom.[1][2]

Dopaminski receptor D3
Dopaminski D3 receptor sa etiklopridom (PDB 3PBL​)
Dostupne strukture
3PBL
Identifikatori
Simboli DRD3; D3DR; ETM1; FET1
Vanjski ID OMIM126451 MGI94925 HomoloGene623 IUPHAR: D3 GeneCards: DRD3 Gene
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 1814 13490
Ensembl ENSG00000151577 ENSMUSG00000022705
UniProt P35462 P30728
RefSeq (mRNA) NM_000796.3 NM_007877.1
RefSeq (protein) NP_000787.2 NP_031903.1
Lokacija (UCSC) Chr 3:
113.85 - 113.92 Mb
Chr 16:
43.76 - 43.82 Mb
PubMed pretraga [1] [2]

D3 podtip dopaminskog receptora inhibira adenilil ciklazu putem inhibicije G proteina. Ovaj receptor je izražen u filogenetički starijim regionima mozga, što sugeriše da on ima ulogu u kognitivnim i emocionim funkcijama. On je meta za lekove kojima se tretira šizofrenija, addikcija, i Parkinsonova bolest[3] . Alternativno splajsovanje ovog gena proizvodi višestruke transkriptne varijante koje mogu da koriraju različite izoforme, mada neke varijante mogu da budu bez funkcije.[2]

D3 agonisti poput 7-OH-DPAT, pramipeksola, i rotigotina, pokazuju antidepresantne efekte u modelima na glodarima za depresiju.[4][5]

Brojni neselektivni lekovi na recept se vezuju za D3 receptor. Među njima su neki od novijih dopaminskih agonista koji se koriste za lečenje Parkinsonove bolesti, npr. pramipeksol i ropinirol, koji se takođe vezuju za D2 i nemaju jaku selektivnost.

Agonisti

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  • 8-OH-PBZI (cis-8-Hidroksi-3-(n-propil)-1,2,3a,4,5,9b-heksahidro-1H-benz[e]indol)
  • PF-219,061 ((R)-3-(4-Propilmorfolin-2-il)fenol): >1000-puta funkcionalna (efikasnost) selektivnost u odnosu na D2[6]
  • jedinjenje R,R-16: 250x selektivnost vezivanja u odnosu na D2[7]
  • trans-N4-[4-(2,3-Dihlorofenil)-1-piperazinil]cikloheksil3-metoksibenzamid, pun agonist, > 200-puta selektivniji u odnosu na D4, D2, 5-HT1A, i α1-receptore[8]
  • (-)-7[2-(4-Fenilpiperazin-1-il)etil]propilamino5,6,7,8-tetrahidronaftalen-2-ol[9]
  • BP-897: parcijalni agonist[10]
  • FAUC 73
  • FAUC 460: parcijalni agonist, dobar afinitet i selektivnost[11]
  • FAUC 346: parcijalni agonist, podtip selektivan[12]
  • PD-128,907
  • jedinjenje 12: parcijalni agonist, Ki = 0.41nM, 800x selektivnost vezivanja u odnosu na D2[13]
  • piribedil[14]

Antagonisti

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  • N-(4-(4-(2,3-Dihloro- ili 2-metoksifenil)piperazin-1-il)butil)heterobiarilkarboksamidi[15]
  • FAUC 365, podtip selektivni antagonist[12]
  • jedinjenje 29[16]
  • Nafadotrid
  • NGB-2904[17]
  • SB-277011-A, selektivni D3 antagonist, 80x selektivniji u odnosu na D2 bez parcijalnog agonističkog dejstva. Koristi se u ispitivanjima za adikcije
  • Domperidon - D2 i D3 antagonist
 
Chemical structures of selective D3 receptor ligands.

Interakcije

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Dopaminski receptor D3 formira interakcije sa CLIC6[18] i EPB41L1.[19]

Vidi još

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Reference

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  1. ^ Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (1991). „Chromosomal localization of the human D3 dopamine receptor gene”. Hum Genet. 87 (5): 618—20. PMID 1916765. 
  2. ^ а б „Entrez Gene: DRD3 dopamine receptor D3”. 
  3. ^ Joyce, JN; Millan, MJ (2007). „Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.”. Current opinion in pharmacology. 7 (1): 100—5. PMID 17174156. 
  4. ^ Breuer ME; Groenink L; Oosting RS (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. PMID 19549514. doi:10.1016/j.ejphar.2009.06.029. 
  5. ^ Bertaina-Anglade V, La Rochelle CD, Scheller DK (2006). „Antidepressant properties of rotigotine in experimental models of depression”. European Journal of Pharmacology. 548 (1-3): 106—14. PMID 16959244. doi:10.1016/j.ejphar.2006.07.022. 
  6. ^ 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. PMID 17976986. doi:10.1016/j.bmcl.2007.10.059. 
  7. ^ 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. PMID 19324548. doi:10.1016/j.bmcl.2009.03.015. 
  8. ^ 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. PMID 16451749. doi:10.1211/jpp.58.2.0008. 
  9. ^ 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]propylamino5,6,7,8-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. PMID 18072730. doi:10.1021/jm070860r. 
  10. ^ Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby CR, Heidbreder C, Gaál J, Gardner EL (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. PMID 17985117. doi:10.1007/s00213-007-0986-6. 
  11. ^ 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. PMID 18834111. doi:10.1021/jm800895v. 
  12. ^ а б 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. PMID 12361386. doi:10.1021/jm025558r. 
  13. ^ Chen J; Collins GT; Zhang J (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. PMC 2662387 . PMID 18785726. doi:10.1021/jm800471h. 
  14. ^ Cagnotto A, Parotti L, Mennini T (1996). „In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study”. Eur. J. Pharmacol. 313 (1-2): 63—7. PMID 8905329. doi:10.1016/0014-2999(96)00503-1. 
  15. ^ Newman AH; Grundt P; Cyriac G (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. PMC 2760932 . PMID 19331412. doi:10.1021/jm900095y. 
  16. ^ {{cite journal |author1=Grundt P |author2=Carlson EE |author3=Cao J |display-editors=etal |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=J. Med. Chem. |volume=48 |issue=3 |pages=839–48 |year=2005 |pmid=15689168 |doi=10.1021/jm049465g |url=}}
  17. ^ 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. PMID 17627675. doi:10.1111/j.1527-3458.2007.00013.x. 
  18. ^ Griffon, Nathalie; Jeanneteau Freddy (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. doi:10.1016/S0169-328X(03)00283-3. 
  19. ^ Binda, Alicia V; Kabbani Nadine (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. doi:10.1124/mol.62.3.507. 

Literatura

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Spoljašnje veze

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