Unlike the histamine receptors discovered earlier, H4 was found in 2000 through a search of the human genomic DNA data base.[8]
Tissue distributionedit
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.[9] It was also found that H4 receptor exhibits a uniform expression pattern in the human oral epithelium.[10]
Functionedit
The Histamine H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis.[11] This occurs via the βγ subunit acting at phospholipase C to cause actin polymerization and eventually chemotaxis.[11]
The histamine H4 receptor has been identified as a vital regulator of the immune system, involved in eosinophil migration, mast cell recruitment, dendritic cell activation, and T cell differentiation. The discovery of this receptor has brought it to increasing attention for its therapeutic use in inflammatory diseases such as allergy, asthma, chronic itch, and autoimmune diseases.[12]
Structureedit
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[13] was built by homology modelling based on the crystal structure of bovine rhodopsin.[14] 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.[15]
Recent advancements in GPCR crystallization, in particular the determination of the human histamine H1 receptor in complex with doxepin[16] will likely increase the quality of novel structural H4 receptor models.[17][18]
Ligandsedit
Although the effectiveness of H4 receptor ligands has been studied in animal models and human biological samples, further research is needed to understand genetic polymorphisms and interspecies differences in their actions and pharmacological characteristics.[12]
The available data support the H4 receptor as a promising new drug target for modulating histamine-mediated immune signaling and offer optimistic prospects for developing new therapies for inflammatory diseases.[12]
^ abcGRCh38: Ensembl release 89: ENSG00000134489 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000037346 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^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.
^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. doi:10.1124/mol.59.3.427. PMID 11179435.
^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): 36781–36786. doi:10.1074/jbc.M006480200. PMID 10973974.
^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. S2CID 6698467.
^Salem A, Rozov S, Al-Samadi A, et al. Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus. Br J Dermatol. 2016. Available at: https://dx.doi.org/10.1111/bjd.14995.
^ abcZampeli E, Tiligada E (May 2009). "The role of histamine H4 receptor in immune and inflammatory disorders". Br J Pharmacol. 157 (1): 24–33. doi:10.1111/j.1476-5381.2009.00151.x. PMC2697784. PMID 19309354.
^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. doi:10.1124/mol.62.1.38. PMID 12065753. S2CID 16628657.
^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. Bibcode:2000Sci...289..739P. CiteSeerX10.1.1.1012.2275. doi:10.1126/science.289.5480.739. PMID 10926528.
^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.
Robert Kiss (June 16, 2011). "The road to mcule". Mcule (Blog).
^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): 65–70. doi:10.1038/nature10236. PMC3131495. PMID 21697825.
^Schultes S, Nijmeijer S, Engelhardt H, Kooistra AJ, Vischer HF, de Esch IJ, Haaksma EJ, Leurs R, de Graaf C (2013). "Mapping histamine H4 receptor-ligand binding modes". MedChemComm. 4: 193–204. doi:10.1039/C2MD20212C.
^Nijmeijer S, Engelhardt H, Schultes S, van de Stolpe AC, Lusink V, de Graaf C, Wijtmans M, Haaksma EE, de Esch IJ, Stachurski K, Vischer HF, Leurs R (2013). "Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 98(3.36) of the human histamine H4 receptor". Br J Pharmacol. 170 (1): 89–100. doi:10.1111/bph.12113. PMC3764852. PMID 23347159.
^Varga, C; Horvath, K; Berko, A; Thurmond, RL; Dunford, PJ; Whittle, BJ. (2005). "Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat". European Journal of Pharmacology. 522 (1–3): 130–8. doi:10.1016/j.ejphar.2005.08.045. PMID 16213481.
^Coruzzi, G; Adami, M; Guaita, E; de Esch, IJ; Leurs, R. (2007). "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. 563 (1–3): 240–4. doi:10.1016/j.ejphar.2007.02.026. PMID 17382315.
histamine, receptor, histamine, receptor, like, other, three, histamine, receptors, member, protein, coupled, receptor, superfamily, that, humans, encoded, hrh4, gene, hrh4identifiersaliaseshrh4, axor35, bg26, gpcr105, gprv53, hh4r, histamine, receptor, h4exte. The histamine H4 receptor like the other three histamine receptors is a member of the G protein coupled receptor superfamily that in humans is encoded by the HRH4 gene 5 6 7 HRH4IdentifiersAliasesHRH4 AXOR35 BG26 GPCR105 GPRv53 H4 H4R HH4R histamine receptor H4External IDsOMIM 606792 MGI 2429635 HomoloGene 11002 GeneCards HRH4 OMA HRH4 orthologsGene location Human Chr Chromosome 18 human 1 Band18q11 2Start24 460 637 bp 1 End24 479 961 bp 1 Gene location Mouse Chr Chromosome 18 mouse 2 Band18 18 A1Start13 140 047 bp 2 End13 155 939 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytebone marrowtibialis anterior musclebloodappendixdeltoid muscleduodenumright lobe of liverlymph nodesmooth muscle tissueTop expressed inspermatocytespermatidvastus lateralis muscletesticlethymusMore reference expression dataBioGPSn aGene ontologyMolecular functionG protein coupled receptor activity signal transducer activity histamine receptor activity G protein coupled serotonin receptor activity G protein coupled acetylcholine receptor activity neurotransmitter receptor activityCellular componentintegral component of membrane membrane plasma membrane integral component of plasma membrane dendriteBiological processpositive regulation of cytosolic calcium ion concentration regulation of MAPK cascade signal transduction inflammatory response negative regulation of adenylate cyclase activity G protein coupled receptor signaling pathway biological process G protein coupled receptor signaling pathway coupled to cyclic nucleotide second messenger adenylate cyclase inhibiting G protein coupled acetylcholine receptor signaling pathway chemical synaptic transmission G protein coupled serotonin receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez59340225192EnsemblENSG00000134489ENSMUSG00000037346UniProtQ9H3N8Q91ZY2RefSeq mRNA NM 001143828NM 001160166NM 021624NM 153087RefSeq protein NP 001137300NP 001153638NP 067637NP 694727Location UCSC Chr 18 24 46 24 48 MbChr 18 13 14 13 16 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Discovery 2 Tissue distribution 3 Function 4 Structure 5 Ligands 5 1 Agonists 5 2 Antagonists 5 3 Therapeutic potential 6 See also 7 References 8 External linksDiscovery editUnlike the histamine receptors discovered earlier H4 was found in 2000 through a search of the human genomic DNA data base 8 Tissue distribution editH4 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 9 It was also found that H4 receptor exhibits a uniform expression pattern in the human oral epithelium 10 Function editThe Histamine H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis 11 This occurs via the bg subunit acting at phospholipase C to cause actin polymerization and eventually chemotaxis 11 The histamine H4 receptor has been identified as a vital regulator of the immune system involved in eosinophil migration mast cell recruitment dendritic cell activation and T cell differentiation The discovery of this receptor has brought it to increasing attention for its therapeutic use in inflammatory diseases such as allergy asthma chronic itch and autoimmune diseases 12 Structure editThe 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 13 was built by homology modelling based on the crystal structure of bovine rhodopsin 14 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 15 Recent advancements in GPCR crystallization in particular the determination of the human histamine H1 receptor in complex with doxepin 16 will likely increase the quality of novel structural H4 receptor models 17 18 Ligands editAlthough the effectiveness of H4 receptor ligands has been studied in animal models and human biological samples further research is needed to understand genetic polymorphisms and interspecies differences in their actions and pharmacological characteristics 12 Agonists edit 4 Methylhistamine VUF 8430 2 Aminoiminomethyl amino ethyl carbamimidothioic acid ester OUP 16 Clozapine JNJ 28610244 Antagonists edit Toreforant JNJ 38518168 Mianserin also a H1 and H3 antagonist Thioperamide also a selective H3 antagonist JNJ 7777120 discontinued JNJ 39758979 discontinued ZPL389 VUF 6002 1 5 Chloro 1H benzimidazol 2 yl carbonyl 4 methylpiperazine A987306 A943931 Pimozide Therapeutic potential edit The available data support the H4 receptor as a promising new drug target for modulating histamine mediated immune signaling and offer optimistic prospects for developing new therapies for inflammatory diseases 12 H4 receptor antagonists could be used to treat asthma and allergies 19 The highly selective histamine H4 antagonist VUF 6002 is orally active and inhibits the activity of both mast cells and eosinophils in vivo 20 and has anti inflammatory and antihyperalgesic effects 21 See also editHistamine H1 receptor Histamine H2 receptor Histamine H3 receptorReferences edit a b c GRCh38 Ensembl release 89 ENSG00000134489 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000037346 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 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 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 doi 10 1124 mol 59 3 427 PMID 11179435 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 36786 doi 10 1074 jbc M006480200 PMID 10973974 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 S2CID 6698467 Salem A Rozov S Al Samadi A et al Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus Br J Dermatol 2016 Available at https dx doi org 10 1111 bjd 14995 a b 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 S2CID 14932773 a b c Zampeli E Tiligada E May 2009 The role of histamine H4 receptor in immune and inflammatory disorders Br J Pharmacol 157 1 24 33 doi 10 1111 j 1476 5381 2009 00151 x PMC 2697784 PMID 19309354 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 doi 10 1124 mol 62 1 38 PMID 12065753 S2CID 16628657 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 Bibcode 2000Sci 289 739P CiteSeerX 10 1 1 1012 2275 doi 10 1126 science 289 5480 739 PMID 10926528 Kiss R Kiss B Konczol A Szalai F Jelinek I Laszlo V Noszal 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 Robert Kiss June 16 2011 The road to mcule Mcule Blog 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 65 70 doi 10 1038 nature10236 PMC 3131495 PMID 21697825 Schultes S Nijmeijer S Engelhardt H Kooistra AJ Vischer HF de Esch IJ Haaksma EJ Leurs R de Graaf C 2013 Mapping histamine H4 receptor ligand binding modes MedChemComm 4 193 204 doi 10 1039 C2MD20212C Nijmeijer S Engelhardt H Schultes S van de Stolpe AC Lusink V de Graaf C Wijtmans M Haaksma EE de Esch IJ Stachurski K Vischer HF Leurs R 2013 Design and pharmacological characterization of VUF14480 a covalent partial agonist that interacts with cysteine 98 3 36 of the human histamine H4 receptor Br J Pharmacol 170 1 89 100 doi 10 1111 bph 12113 PMC 3764852 PMID 23347159 InterPro IPR008102 Histamine H4 receptor Varga C Horvath K Berko A Thurmond RL Dunford PJ Whittle BJ 2005 Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat European Journal of Pharmacology 522 1 3 130 8 doi 10 1016 j ejphar 2005 08 045 PMID 16213481 Coruzzi G Adami M Guaita E de Esch IJ Leurs R 2007 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 563 1 3 240 4 doi 10 1016 j ejphar 2007 02 026 PMID 17382315 External links editHRH4 protein human at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Histamine H4 receptor amp oldid 1191988756, wikipedia, wiki, book, books, library,
