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Pretraga

Dopaminski receptor D4

Izvor: Wikipedija
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Dopaminski receptor D4
Identifikatori
SimboliDRD4; D4DR
Vanjski IDOMIM126452MGI94926HomoloGene20215IUPHAR:D4GeneCards:DRD4 Gene
Ontologija gena
Molekularna funkcijaaktivnost dopaminskog receptora, spregnutog sa Gi/Goaktivnost prenosa signalareceptorska aktivnostaktivnost G-protein spregnutog receptoraaktivnost dopaminskog receptoraproteinsko vezivanjevezivanje lekovaregulacija aktivnosti kalijumovog kanalavezivanje za SH3 domendopaminsko vezivanje
Celularna komponentacitoplazmaćelijska membranaintegralno sa ćelijskom membranomćelijski korteksvezikularna membranamembranaaksonneuronsko ćelijsko telo
Biološki procesaktivacija MAPK aktivnostirespons na strahdopaminergička sinaptička transmisijarespons na amfetaminhomeostaza ćelijskih jona kalcijumanegativna regulacija aktivnosti adenilat ciklazeinhibicija aktivnosti adenilat ciklaze signalnim putem dopaminskog receptorasignalni put dopaminskog receptorakratkotrajna memorijalokomotorno ponašanje odrasliholfaktorno učenje
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez181513491
EnsemblENSG00000069696ENSMUSG00000025496
UniProtP21917P51436
RefSeq (mRNA)NM_000797.3NM_007878.2
RefSeq (protein)NP_000788.2NP_031904.1
Lokacija (UCSC)Chr 11:
0.64 - 0.64 Mb
Chr 7:
148.48 - 148.48 Mb
PubMed pretraga[1][2]

Dopaminski receptor D4 jeG protein spregnuti receptor kodiranDRD4 genom.[1] Poput drugihdopaminskih receptora, D4 receptor se aktiviraneurotransmiteromdopaminom. On je povezan sa mnogim neurološkim i psihijatrijskim oboljenjima, neka od kojih sušizofrenija,Parkinsonova bolest,bipolarni poremećaj,adikcije, iporemećaji ishrane kao što suanoreksija nervoza,bulimija nervoza i nekontrolisano jedenje.

D4 jebiološka meta za lekove kojima se tretirašizofrenija iParkinsonova bolest. Ovaj receptor je sličan saD2 receptorom, u smislu da aktivirani receptor inhibira enzimadenilat cilazu, čime se redukuje intraćelijska koncentracija sekundarnog glasnikacikličnog AMP-a.[2]

Ligandi

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Hemijske strukture reprezentativnih D4 liganda.

Agonisti

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  • WAY-100635: potentan puniagonist, sa 5-HT1A antagonistnom komponentom[3]
  • A-412,997: pun agonist, > 100-puta selektivniji u odnosu na panel od sedamdeset različitih receptora i jonskih kanala[4]
  • ABT-724 - razvijen za lečenje impotencije[5]
  • ABT-670 - ima bolju oralnu biodostupnost od ABT-724[6]
  • FAUC 316: parcijalni agonist, > 8600-puta selektivniji u odnosu na druge dopaminske receptore[7]
  • FAUC 299: parcijalni agonist[7]
  • (E)-1-aril-3-(4-piridinpiperazin-1-il)propanon oksimi[8]
  • PIP3EA: parcijalni agonist[9]
  • Flibanzerin - parcijalni agonist
  • PD-168,077 - D4 selektivan, ali se isto tako vezuje za α1A, α2C i 5HT1A
  • CP-226,269 - D4 selektivan, ali se isto tako vezuje za D2, D3, α2A, α2C i 5HT1A
  • Ro10-5824 - parcijalni agonist

Antagonisti

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Inverzni agonisti

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Reference

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  1. Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (April 1991). „Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine”. Nature 350 (6319): 610–4. DOI:10.1038/350610a0. PMID 1840645. 
  2. Neve KA, Seamans JK, Trantham-Davidson H (August 2004). „Dopamine receptor signaling”. J. Recept. Signal Transduct. Res. 24 (3): 165–205. DOI:10.1081/RRS-200029981. PMID 15521361. 
  3. Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE (2006). „WAY-100635 is a potent dopamine D4 receptor agonist”. Psychopharmacology (Berl.) 188 (2): 244–51. DOI:10.1007/s00213-006-0490-4. PMID 16915381. 
  4. Moreland RB, Patel M, Hsieh GC, Wetter JM, Marsh K, Brioni JD (2005). „A-412997 is a selective dopamine D4 receptor agonist in rats”. Pharmacol. Biochem. Behav. 82 (1): 140–7. DOI:10.1016/j.pbb.2005.08.001. PMID 16153699. 
  5. Cowart M, Latshaw SP, Bhatia P, Daanen JF, Rohde J, Nelson SL, Patel M, Kolasa T, Nakane M, Uchic ME, Miller LN, Terranova MA, Chang R, Donnelly-Roberts DL, Namovic MT, Hollingsworth PR, Martino BR, Lynch JJ, Sullivan JP, Hsieh GC, Moreland RB, Brioni JD, Stewart AO (July 2004). „Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a dopaminergic agent with a novel mode of action for the potential treatment of erectile dysfunction”. Journal of Medicinal Chemistry 47 (15): 3853–64. DOI:10.1021/jm030505a. PMID 15239663. 
  6. Patel MV, Kolasa T, Mortell K,et al. (December 2006). „Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction”. J. Med. Chem. 49 (25): 7450–65. DOI:10.1021/jm060662k. PMID 17149874. 
  7. 7,07,1Hübner H, Kraxner J, Gmeiner P (2000). „Cyanoindole derivatives as highly selective dopamine D4 receptor partial agonists: solid-phase synthesis, binding assays, and functional experiments”. J. Med. Chem. 43 (23): 4563–9. DOI:10.1021/jm0009989. PMID 11087581. 
  8. Kolasa T, Matulenko MA, Hakeem AA,et al. (August 2006). „1-aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one oximes as potent dopamine D4 receptor agonists for the treatment of erectile dysfunction”. J. Med. Chem. 49 (17): 5093–109. DOI:10.1021/jm060279f. PMID 16913699. 
  9. Enguehard-Gueiffier C, Hübner H, El Hakmaoui A,et al. (June 2006). „2-[(4-phenylpiperazin-1-yl)methyl]imidazo(di)azines as selective D4-ligands. Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a potent and selective D4 partial agonist”. J. Med. Chem. 49 (13): 3938–47. DOI:10.1021/jm060166w. PMID 16789750. 
  10. Nakane M, Cowart MD, Hsieh GC,et al. (July 2005). „2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist”. Neuropharmacology 49 (1): 112–21. DOI:10.1016/j.neuropharm.2005.02.004. PMID 15992586. 
  11. 11,011,1Prante O, Tietze R, Hocke C, Löber S, Hübner H, Kuwert T, Gmeiner P (2008). „Synthesis, Radiofluorination, and In Vitro Evaluation of Pyrazolo[1,5-a]pyridine-Based Dopamine D4 Receptor Ligands: Discovery of an Inverse Agonist Radioligand for PET”. J. Med. Chem. 51 (6): 1800–10. DOI:10.1021/jm701375u. PMID 18307287. 
  12. Kulagowski JJ, Broughton HB, Curtis NR,et al. (May 1996). „3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor”. J. Med. Chem. 39 (10): 1941–2. DOI:10.1021/jm9600712. PMID 8642550. 
  13. Patel S, Freedman S, Chapman KL,et al. (1 November 1997). „Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor”. J. Pharmacol. Exp. Ther. 283 (2): 636–47. PMID 9353380. 
  14. Patel S, Patel S, Marwood R,et al. (December 1996). „Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor”. Mol. Pharmacol. 50 (6): 1658–64. PMID 8967990. [mrtav link]
  15. Millan MJ, Newman-Tancredi A, Brocco M, Gobert A, Lejeune F, Audinot V, Rivet JM, Schreiber R, Dekeyne A, Spedding M, Nicolas JP, Peglion JL (1998-10-01). „ S 18126 ([2-[4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)piperazin-1-yl methyl]indan-2-yl]), a potent, selective and competitive antagonist at dopamine D4 receptors: an in vitro and in vivo comparison with L 745,870 (3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1H-pyrrolo[2, 3b]pyridine) and raclopride”. J. Pharmacol. Exp. Ther. 287 (1): 167–86. PMID 9765336. Arhivirano izoriginala na datum 2003-07-12. Pristupljeno 2014-05-03. 
  16. Lanig H, Utz W, Gmeiner P (2001). „Comparative molecular field analysis of dopamine D4 receptor antagonists including 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 113), 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-1H-pyrrolo-[2,3-b]pyridine (L-745,870), and clozapine”. J. Med. Chem. 44 (8): 1151–7. DOI:10.1021/jm001055e. PMID 11312915. 

Vanjske veze

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Povezano

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Klasa A:Rodopsinu slični
α1 (A,B,D) • α2 (A,B,C) • β1 • β2 • β3
(svi osim 5-HT3)5-HT1 (A,B,D,E,F) • 5-HT2 (A,B,C) • 5-HT (4,5A,6,7)
Drugi
Acetilholin (M1,M2,M3,M4,M5) • Dopamin (D1,D2,D3,D4,D5) • Histamin (H1,H2,H3,H4) • Melatonin (1A,1B,1C) • TAAR (1,2,3,5,6,8,9)
Metaboliti i
signalni molekuli
CysLT (1,2) • LTB4 (1,2) • FPRL1 • OXE • Prostaglandin (DP (1,2),EP (1,2,3,4),FP) • Prostaciklin • Tromboksan
Drugi
Peptid
B/W (1,2) • FF (1,2) • S • Y (1,2,4,5) • Neuromedin (B,U (1,2)) • Neurotenzin (1,2)
Drugi
Razno
Drugi
Klasa B:Sekretinu slični
Drugi
Klasa C:Metabotropni
glutamat /feromon
TAS1R (1,2,3) • TAS2R (1,3,4,5,8,9,10,12,13,14,16,19,20,30,31,38,39,40,41,42,43,45,46,50)
Drugi
Klasa F:
Frizzled /Zaglađeni
Uvojiti
Zaglađeni
Izvor:https://sh.wikipedia.org/w/index.php?title=Dopaminski_receptor_D4&oldid=42552368
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