Dopaminski receptor D₃

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

edit

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

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-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-HT_1A, 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, K_i = 0.41nM, 800x selektivnost vezivanja u odnosu na D₂^[13]
piribedil^[14]

Antagonisti

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

Interakcije

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

Reference

↑ 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.
↑ ^2,0 ^2,1 „Entrez Gene: DRD3 dopamine receptor D3”.
↑ 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.
↑ Breuer ME, Groenink L, Oosting RS, 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ ^12,0 ^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.
↑ 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 2662387. PMID 18785726.
↑ 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.
↑ 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 2760932. PMID 19331412.
↑ Grundt P, Carlson EE, Cao J, et al. Novel heterocyclic trans olefin analogues of N4-[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=}}
↑ 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.
↑ Griffon, Nathalie; Jeanneteau Freddy, Prieur Fanny, Diaz Jorge, Sokoloff Pierre (September 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.
↑ Binda, Alicia V; Kabbani Nadine, Lin Ridwan, Levenson Robert (September 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

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 47477. 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 14638. 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 33197. 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.

Povezano

Dopaminski receptor

Spoljašnje veze

„Dopamine Receptors: D₃”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.
MeSH Receptors,+Dopamine+D3

[pmid1916765-1] 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.

[entrez-2] 2,0 ^2,1 „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.

[pmid19549514-4] Breuer ME, Groenink L, Oosting RS, 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.

[pmid16959244-5] 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.

[pmid17976986-6] 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.

[pmid19324548-7] 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.

[pmid16451749-8] 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.

[pmid18072730-9] 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.

[pmid17985117-10] 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.

[pmid18834111-11] 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.

[pmid12361386-12] 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.

[pmid18785726-13] 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 2662387. PMID 18785726.

[pmid8905329-14] 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.

[pmid19331412-15] 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 2760932. PMID 19331412.

[pmid15689168-16] Grundt P, Carlson EE, Cao J, et al. Novel heterocyclic trans olefin analogues of N4-[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=}}

[pmid17627675-17] 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.

[pmid14499480-18] Griffon, Nathalie; Jeanneteau Freddy, Prieur Fanny, Diaz Jorge, Sokoloff Pierre (September 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.

[pmid12181426-19] Binda, Alicia V; Kabbani Nadine, Lin Ridwan, Levenson Robert (September 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.

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