Dopaminski receptor D3

Из Википедије, слободне енциклопедије
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
PBB GE DRD3 211625 s at tn.png
PBB GE DRD3 214559 at tn.png
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 dopaminski receptor je protein koji je kod ljudi kodiran DRD3 genom.[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]

Ligandi[уреди]

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[уреди]

  • 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[уреди]

  • 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[уреди]

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

Reference[уреди]

  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. 2,0 2,1 „Entrez Gene: DRD3 dopamine receptor D3”. 
  3. Joyce, JN; Millan, MJ (2007 Feb). „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; et al. (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 (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. 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. 
  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. doi:10.1016/j.bmcl.2009.03.015. PMID 19324548. 
  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. doi:10.1211/jpp.58.2.0008. PMID 16451749. 
  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. doi:10.1021/jm070860r. PMID 18072730. 
  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. doi:10.1007/s00213-007-0986-6. PMID 17985117. 
  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. doi:10.1021/jm800895v. PMID 18834111. 
  12. 12,0 12,1 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. 
  13. 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. PMC 2662387слободно за читање. PMID 18785726. 
  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. doi:10.1016/0014-2999(96)00503-1. PMID 8905329. 
  15. 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 (8): 2559. doi:10.1021/jm900095y. PMC 2760932слободно за читање. PMID 19331412. 
  16. 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. 
  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. doi:10.1111/j.1527-3458.2007.00013.x. PMID 17627675. 
  18. Griffon, Nathalie; Jeanneteau Freddy, Prieur Fanny, Diaz Jorge, Sokoloff Pierre (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. doi:10.1016/S0169-328X(03)00283-3. ISSN 0169-328X. PMID 14499480. 
  19. Binda, Alicia V; Kabbani Nadine, Lin Ridwan, Levenson Robert (2002). „D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N”. Mol. Pharmacol. United States. 62 (3): 507—13. doi:10.1124/mol.62.3.507. ISSN 0026-895X. PMID 12181426. 

Literatura[уреди]

  • 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. PMC 47477слободно за читање. 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. PMC 14638слободно за читање. 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. PMC 33197слободно за читање. 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. 

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