Dopaminski receptor D4
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Dopaminski receptor D4 | |||||||||||
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Identifikatori | |||||||||||
Simboli | DRD4; D4DR | ||||||||||
Vanjski ID | OMIM: 126452 MGI: 94926 HomoloGene: 20215 IUPHAR: D4 GeneCards: DRD4 Gene | ||||||||||
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Pregled RNK izražavanja | |||||||||||
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podaci | |||||||||||
Ortolozi | |||||||||||
Vrsta | Čovek | Miš | |||||||||
Entrez | 1815 | 13491 | |||||||||
Ensembl | ENSG00000069696 | ENSMUSG00000025496 | |||||||||
UniProt | P21917 | P51436 | |||||||||
RefSeq (mRNA) | NM_000797.3 | NM_007878.2 | |||||||||
RefSeq (protein) | NP_000788.2 | NP_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 je G protein spregnuti receptor kodiran DRD4 genom.[1] Poput drugih dopaminskih receptora, D4 receptor se aktivira neurotransmiterom dopaminom. On je povezan sa mnogim neurološkim i psihijatrijskim oboljenjima, neka od kojih su šizofrenija, Parkinsonova bolest, bipolarni poremećaj, adikcije, i poremećaji ishrane kao što su anoreksija nervoza, bulimija nervoza i nekontrolisano jedenje.
D4 je biološka meta za lekove kojima se tretira šizofrenija i Parkinsonova bolest. Ovaj receptor je sličan sa D2 receptorom, u smislu da aktivirani receptor inhibira enzim adenilat cilazu, čime se redukuje intraćelijska koncentracija sekundarnog glasnika cikličnog AMP-a.[2]
Ligandi
![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b5/D4_ligands.png/400px-D4_ligands.png)
Agonisti
- WAY-100635: potentan puni agonist, 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
- A-381393: potentan, podtip selektivan antagonist (>2700-puta)[10]
- FAUC 213[11]
- L-745,870[12][13]
- L-750,667[14]
- S 18126: takođe σ1 afin[15]
- Fananserin - mešoviti 5-HT2A / D4 antagonist
Inverzni agonisti
- FAUC F41: inverzni agonist, podtip selektivan u odnosu na D2 i D3[11][16]
Reference
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 7,0 7,1 Hübner 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 11,0 11,1 Prante 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.
- ↑ 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.
- ↑ 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.
- ↑ 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]
- ↑ 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 iz originala na datum 2003-07-12. Pristupljeno 2014-05-03.
- ↑ 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.
Spoljašnje veze
- „Dopamine Receptors: D4”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2012-03-05.
- Istraživanja DRD4 gena
- MeSH Receptors,+Dopamine+D4
- Marisa Wilson. „Are you a thrill seeker??”. Davidson College. Pristupljeno 05. 04. 2008.
- „The D4DR Gene”. D4DR Club. Arhivirano iz originala na datum 2007-10-13. Pristupljeno 05. 04. 2008.
Povezano
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Drugi | Moždano specifični angiogenezni inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1, 2) • EMR (1, 2, 3) • Glukagon (GR, GIPR, GLP1R, GLP2R) • Hormon rasta oslobađajući hormon • PACAPR1 • GPR • Latrofilin (1, 2, 3, ELTD1) • Metuselah-slični proteini • Paratiroidni hormon (1, 2) • Sekretin • Vazoaktivni intestinalni peptid (1, 2) |
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glutamat / feromon
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Frizzled / Zaglađeni
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Zaglađeni |
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)