Histaminski H₄ receptor

Histaminski receptor H4
Histaminski receptor H4
Identifikatori
Simboli	HRH4; AXOR35; BG26; GPCR105; GPRv53; H4; H4R; HH4R
Vanjski ID	OMIM: 606792 MGI: 2429635 HomoloGene: 11002 IUPHAR: H4 GeneCards: HRH4 Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosa signala; • receptorska aktivnost; • aktivnost G protein spregnutog receptora; • aktivnost histaminskog receptora;
Celularna komponenta	• membranska frakcija; • ćelijska membrana; • integralno sa membranom;
Biološki proces	• inflamatorni respons; • biološki proces;
Ortolozi
Vrsta	Čovek
Entrez	59340
Ensembl	ENSG00000134489
UniProt	Q9H3N8
RefSeq (mRNA)	NM_001143828.1
RefSeq (protein)	NP_001137300.1
Lokacija (UCSC)	Chr 18:; 22.04 - 22.06 Mb
PubMed pretraga	[1]

Histaminski H₄ receptor je član familije G protein spregnutih receptora.^[1]^[2]^[3]

Distribucija u tkivu

H₄ je visoko izražen u koštanoj srži i belim krvnim zrncima. On reguliše otpuštanje neutrofila iz kičmene moždine i naknadnu infiltraciju u zimosanom indukovanom mišjem modelu zapaljenja plućne maramice.^[4] On je takođe izražen u crevima, jetri, plućima, slezini, testisima, timusu, krajnicima, i dušniku.^[5]

Funkcija

Pokazano je da H₄ posreduje hemotaksu mastocita.^[6] Smatra se da do toga dolazi putem mehanizma G_i spregnutog smanjenja cAMP.^[7]

Struktura

3D struktura H₄ receptora nije rešena usled problema vezanih za GPCR kristalizaciju. Razvijen je niz strukturnih modela H₄ receptora za različite svrhe. Prvi model H₄ receptora^[8] je formiran putem homolognog modelovanja baziranog na kristalnoj strukturi goveđeg rodopsina.^[9] Taj model je korišten za interpretaciju podataka mutageneze pojedinih mesta sekvence, čime je otkriven značaj Asp94 (3.32) i Glu182 (5.46) ostataka za vezivanje liganda i aktivaciju receptora.

Drugi strukturni model H₄ receptora baziran na rodopsinu je uspešno korišten za identifikaciju novih liganda.^[10]

Nedavni progres u GPCR kristalizaciji, posebno određivanje strukture ljudskog histaminskog H₁ receptora u kompleksu sa doksepinom^[11] će uticati na poboljšanje kvaliteta novih strukturnih modela H₄ receptora.

Ligandi

Agonisti

4-Metilhistamin
VUF-8430 (2-[(Aminoiminometil)amino]etil estar karbamimidotionske kiseline)
OUP-16

Antagonisti

Tioperamid
JNJ 7777120
VUF-6002 (1-[(5-hloro-1H-benzimidazol-2-il)karbonil]-4-metilpiperazin)
A987306
A943931

Terapeutski potencijal

Inhibicija H₄ receptora se može koristiti u tretiranju astme i alergije.^[7]

Visoko selektivni antagonist histaminskog H₄ receptora VUF-6002 je oralno aktivan i inhibira aktivnost mastocita i eozinofila in vivo.^[12] On ima antiinflamatorne i antihiperalgezivne efekte.^[13]

Reference

^ Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S (2000). „Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes”. J. Biol. Chem. 275 (47): 36781—6. PMID 10973974. doi:10.1074/jbc.M006480200.
^ Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K (2000). „Molecular cloning and characterization of a new human histamine receptor, HH4R”. Biochem. Biophys. Res. Commun. 279 (2): 615—20. PMID 11118334. doi:10.1006/bbrc.2000.4008.
^ Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF (2001). „Discovery of a novel member of the histamine receptor family”. Mol. Pharmacol. 59 (3): 427—33. PMID 11179435. Архивирано из оригинала (abstract) 07. 10. 2008. г. Приступљено 05. 07. 2012.
^ Takeshita K, Bacon KB, Gantner F (2004). „Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan”. J. Pharmacol. Exp. Ther. 310 (1): 272—80. PMID 14996947. doi:10.1124/jpet.103.063776.
^ Bioreagents.com: Histamine H4 Receptor
^ Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP (2003). „Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells”. J. Pharmacol. Exp. Ther. 305 (3): 1212—21. PMID 12626656. doi:10.1124/jpet.102.046581.
^ ^а ^б InterPro: IPR008102 Histamine H4 receptor
^ Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ (2002). „Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor”. Mol. Pharmacol. 62 (1): 38—47. PMID 12065753.
^ Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000). „Crystal structure of rhodopsin: A G protein-coupled receptor”. Science. 289 (5480): 739—45. PMID 10926528. doi:10.1126/science.289.5480.739.
^ Kiss R, Kiss B, Könczöl A, Szalai F, Jelinek I, László V, Noszál B, Falus A, Keseru GM (2008). „Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening”. J. Med. Chem. 51 (11): 3145—53. PMID 18459760. doi:10.1021/jm7014777. Генерални сажетак – blog.mcule.com.
^ Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (2011). „Structure of the human histamine H(1) receptor complex with doxepin”. Nature. 475 (7354). PMID 21697825. doi:10.1038/nature10236.
^ Varga C, Horvath K, Berko A, Thurmond RL, Dunford PJ, Whittle BJ. Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. European Journal of Pharmacology. 2005 Oct 17;522(1-3):130-8. PMID 16213481
^ Coruzzi G, Adami M, Guaita E, de Esch IJ, Leurs R. Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation.European Journal of Pharmacology. 2007 Jun 1;563(1-3):240-4. PMID 17382315

Spoljašnje veze

HRH4+protein,+human на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid10973974-1] Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S (2000). „Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes”. J. Biol. Chem. 275 (47): 36781—6. PMID 10973974. doi:10.1074/jbc.M006480200.

[pmid11118334-2] Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K (2000). „Molecular cloning and characterization of a new human histamine receptor, HH4R”. Biochem. Biophys. Res. Commun. 279 (2): 615—20. PMID 11118334. doi:10.1006/bbrc.2000.4008.

[pmid11179435-3] Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF (2001). „Discovery of a novel member of the histamine receptor family”. Mol. Pharmacol. 59 (3): 427—33. PMID 11179435. Архивирано из оригинала (abstract) 07. 10. 2008. г. Приступљено 05. 07. 2012.

[pmid14996947-4] Takeshita K, Bacon KB, Gantner F (2004). „Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan”. J. Pharmacol. Exp. Ther. 310 (1): 272—80. PMID 14996947. doi:10.1124/jpet.103.063776.

[otherorgans-5] Bioreagents.com: Histamine H4 Receptor

[pmid12626656-6] Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP (2003). „Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells”. J. Pharmacol. Exp. Ther. 305 (3): 1212—21. PMID 12626656. doi:10.1124/jpet.102.046581.

[interpro-7] а ^б InterPro: IPR008102 Histamine H4 receptor

[pmid12065753-8] Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ (2002). „Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor”. Mol. Pharmacol. 62 (1): 38—47. PMID 12065753.

[pmid10926528-9] Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000). „Crystal structure of rhodopsin: A G protein-coupled receptor”. Science. 289 (5480): 739—45. PMID 10926528. doi:10.1126/science.289.5480.739.

[pmid18459760-10] Kiss R, Kiss B, Könczöl A, Szalai F, Jelinek I, László V, Noszál B, Falus A, Keseru GM (2008). „Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening”. J. Med. Chem. 51 (11): 3145—53. PMID 18459760. doi:10.1021/jm7014777. Генерални сажетак – blog.mcule.com.

[pmid21697825-11] Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (2011). „Structure of the human histamine H(1) receptor complex with doxepin”. Nature. 475 (7354). PMID 21697825. doi:10.1038/nature10236.

[12] Varga C, Horvath K, Berko A, Thurmond RL, Dunford PJ, Whittle BJ. Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. European Journal of Pharmacology. 2005 Oct 17;522(1-3):130-8. PMID 16213481

[13] Coruzzi G, Adami M, Guaita E, de Esch IJ, Leurs R. Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation.European Journal of Pharmacology. 2007 Jun 1;563(1-3):240-4. PMID 17382315

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