Dopaminski receptor D3

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

Dopaminski receptor D3
Dopaminski D3 receptor sa etiklopridom (PDB 3PBL​)
Dostupne strukture
3PBL​
Identifikatori
Simboli	DRD3; D3DR; ETM1; FET1
Vanjski ID	OMIM: 126451 MGI: 94925 HomoloGene: 623 IUPHAR: D3 GeneCards: DRD3 Gene
Ontologija gena Molekularna funkcija • aktivnost dopaminskog receptora, spregnutog sa Gi/Go • aktivnost prenosnika signala • receptorska aktivnost • aktivnost G protein spregnutog receptora • proteinsko vezivanje • vezivanje leka • vezivanje specifično za proteinski domen • dopaminsko vezivanje Celularna komponenta • membranska frakcija • ćelijska membrana • integralno sa ćelijskom membranom • endocitna vezikula • ćelijska projekcija • apični deo ćelije Biološki proces • negativna regulacija transkripcije od promotera RNK polimeraze II • sinaptička transmisija, dopaminergička • response na amfetamin • regulacija krvne zapremine putem renin-angiotenzina • internalizacija G protein spregnutog receptora • ćelijska homeostaza jona kalcijuma • signalni put G-protein spregnutog receptora • aktivacija aktivnosti adenilat ciklaze signalnim putem dopaminskog receptora • negativna regulacija aktivnosti adenilat ciklaze
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

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 , pramipeksola, i rotigotina, pokazuju antidepresantne efekte u modelima na glodarima za depresiju.^[4][5]

Ligandi

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

• (-8-Hidroksi-3-(-propil)-1,2,3a,4,5,9-heksahidro-1-benz[e]indol)
• -3-(4-Propilmorfolin-2-il)fenol): >1000-puta funkcionalna (efikasnost) selektivnost u odnosu na D₂^[6]
• jedinjenje -16: 250x selektivnost vezivanja u odnosu na D₂^[7]
• 3-metoksibenzamid, pun agonist, > 200-puta selektivniji u odnosu na D₄, D₂, , i α1-receptore^[8]
• (-)-75,6,7,8-tetrahidronaftalen-2-ol^[9]
• : parcijalni agonist^[10]
• : parcijalni agonist, dobar afinitet i selektivnost^[11]
• : parcijalni agonist, podtip selektivan^[12]
• jedinjenje 12: parcijalni agonist, , 800x selektivnost vezivanja u odnosu na D₂^[13]
• piribedil^[14]

Antagonisti

• -(4-(4-(2,3-Dihloro- ili 2-metoksifenil)piperazin-1-il)butil)heterobiarilkarboksamidi^[15]
• , podtip selektivni antagonist^[12]
• jedinjenje 29^[16]
• Nafadotrid
• ^[17]
• , 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

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

Vidi još

• Dopaminski receptor

Reference

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. „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 75,6,7,8-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. 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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• Sidhu A, Niznik HB (2000). „Coupling of dopamine receptor subtypes to multiple and diverse G proteins.”. Int. J. Dev. Neurosci. 18 (7): 669—77. PMID 10978845. doi:10.1016/S0736-5748(00)00033-2.
• Sokoloff P; Giros B; Martres MP (1990). „Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.”. Nature. 347 (6289): 146—51. PMID 1975644. doi:10.1038/347146a0.
• 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. PMC 47477 . PMID 8415635. doi:10.1073/pnas.90.19.8942.
• Griffon N; Crocq MA; Pilon C (1996). „Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.”. Am. J. Med. Genet. 67 (1): 63—70. PMID 8678117. doi:10.1002/(SICI)1096-8628(19960216)67:1<63::AID-AJMG11>3.0.CO;2-N.
• 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 (1997). „Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia.”. Am. J. Med. Genet. 74 (1): 40—3. PMID 9034004. doi:10.1002/(SICI)1096-8628(19970221)74:1<40::AID-AJMG9>3.0.CO;2-Z.
• Gulcher JR; Jónsson P; Kong A (1997). „Mapping of a familial essential tremor gene, FET1, to chromosome 3q13.”. Nat. Genet. 17 (1): 84—7. PMID 9288103. doi:10.1038/ng0997-84.
• Oldenhof J; Vickery R; Anafi M (1998). „SH3 binding domains in the dopamine D4 receptor.”. Biochemistry. 37 (45): 15726—36. PMID 9843378. doi:10.1021/bi981634.
• Cargill M; Altshuler D; Ireland J (1999). „Characterization of single-nucleotide polymorphisms in coding regions of human genes.”. Nat. Genet. 22 (3): 231—8. PMID 10391209. doi:10.1038/10290.
• Pilla M; Perachon S; Sautel F (1999). „Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist.”. Nature. 400 (6742): 371—5. PMID 10432116. doi:10.1038/22560.
• Ilani T; Ben-Shachar D; Strous RD (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. PMC 14638 . PMID 11149951. doi:10.1073/pnas.021535398.
• Lin R; Karpa K; Kabbani N (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. PMC 33197 . PMID 11320256. doi:10.1073/pnas.011538198.
• Oldenhof J, Ray A, Vickery R, Van Tol HH (2001). „SH3 ligands in the dopamine D3 receptor.”. Cell. Signal. 13 (6): 411—6. PMID 11384839. doi:10.1016/S0898-6568(01)00157-7.
• Soma M; Nakayama K; Rahmutula D (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.

Spoljašnje veze

• „Dopamine Receptors: D₃”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Receptors,+Dopamine+D3 на ()