Histamine H4 receptor

Histamine receptor H4
Identifiers
Symbols HRH4; AXOR35; BG26; GPCR105; GPRv53; H4; H4R; HH4R; MGC133027
External IDs OMIM: 606792 MGI: 2429635 HomoloGene: 11002 IUPHAR: H4 GeneCards: HRH4 Gene
Orthologs
Species Human Mouse
Entrez 59340 225192
Ensembl ENSG00000134489 ENSMUSG00000037346
UniProt Q9H3N8 Q91ZY2
RefSeq (mRNA) NM_001143828.1 NM_153087.2
RefSeq (protein) NP_001137300.1 NP_694727.1
Location (UCSC) Chr 18:
22.04 – 22.06 Mb		 Chr 18:
13.17 – 13.18 Mb
PubMed search [1] [2]

The histamine H4 receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor superfamily.[1][2][3]

Contents

Tissue distribution

H4 is highly expressed in bone marrow and white blood cells and regulates neutrophil release from bone marrow and subsequent infiltration in the zymosan-induced pleurisy mouse model.[4] It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.[5]

Function

They have been shown to mediate mast cell chemotaxis.[6] It seems to do this by the mechanism of Gi-coupled decrease in cAMP.[7]

Structure

The 3D structure of the H4 receptor has not been solved yet due to the difficulties of GPCR crystallization. Some attempts have been made to develop structural models of the H4 receptor for different purposes. The first H4 receptor model[8] was built by homology modelling based on the crystal structure of bovine rhodopsin.[9] This model was used for the interpretation of site-directed mutagenesis data, which revealed the crucial importance of Asp94 (3.32) and Glu182 (5.46) residues in ligand binding and receptor activation.

A second rhodopsin based structural model of the H4 receptor was successfully used for the identification of novel H4 ligands.[10]

Recent advancements in GPCR crystallization, in particular the determination of the human histamine H1 receptor in complex with doxepin[11] will likely increase the quality of novel structural H4 receptor models.

Ligands

Agonists

Antagonists

Therapeutic potential

By inhibiting the H4 receptor, asthma and allergy may be treated.[7]

The highly selective histamine H4 antagonist VUF-6002 is orally active and inhibits the activity of both mast cells and eosinophils in vivo,[12] and has antiinflammatory and antihyperalgesic effects.[13]

References

  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. doi:10.1074/jbc.M006480200. PMID 10973974. 
  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. doi:10.1006/bbrc.2000.4008. PMID 11118334. 
  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" (abstract). Mol. Pharmacol. 59 (3): 427–33. PMID 11179435. http://molpharm.aspetjournals.org/cgi/content/abstract/59/3/427. 
  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. doi:10.1124/jpet.103.063776. PMID 14996947. 
  5. ^ Bioreagents.com: Histamine H4 Receptor
  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. doi:10.1124/jpet.102.046581. PMID 12626656. 
  7. ^ a b InterPro: IPR008102 Histamine H4 receptor
  8. ^ Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ (July 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. 
  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 (August 2000). "Crystal structure of rhodopsin: A G protein-coupled receptor". Science 289 (5480): 739–45. doi:10.1126/science.289.5480.739. PMID 10926528. 
  10. ^ Kiss R, Kiss B, Könczöl A, Szalai F, Jelinek I, László V, Noszál B, Falus A, Keseru GM (June 2008). "Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening". J. Med. Chem. 51 (11): 3145–53. doi:10.1021/jm7014777. PMID 18459760. Lay summary – blog.mcule.com. 
  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 (June 2011). "Structure of the human histamine H(1) receptor complex with doxepin". Nature 475 (7354). doi:10.1038/nature10236. PMID 21697825. 
  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

External links