Disease relevance of HRH4

• CONCLUSIONS: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases [1].
• Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats [2].
• Our results demonstrate for both NPY5-R and HH4R that the bicistronic vectors with EMCV, VEGF, FGF1A or FGF2 IRES provide clones expressing functional receptors with yields between 25% and 100% [3].
• The histamine H4 receptor in autoimmune disease [4].
• H4R antagonists have been shown to have anti-inflammatory properties and efficacy in a number of disease models, such as those for asthma and colitis in vivo [4].

High impact information on HRH4

• H4R or H2R stimulation suppressed IL-12p70 production in MoDC [5].
• Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells [5].
• We show here that MoDC also express H3R and H4R at the mRNA and protein level. mRNA of the H3R is down-regulated and mRNA of the H4R is up-regulated during the differentiation from monocytes to MoDC [5].
• In comparison to HDAC1, HDAC3 preferentially deacetylated lysines 5 and 12 of H4 and lysine 5 of H2A [6].
• Mammalian cells expressing GPRv53 were demonstrated to bind and respond to histamine in a concentration-dependent manner [7].

Biological context of HRH4

• Tissue distribution analysis revealed that expression of GPRv53 is localized in the peripheral blood leukocytes, spleen, thymus, and colon, which was totally different from the H3 receptor, whose expression was restricted to the brain [7].
• The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18 [8].
• However, both [(35)S]GTPgammaS binding and phosphorylation of mitogen-activated protein kinase were stimulated by histamine via SP9144 activation [9].
• Thus, the description of the H4-receptor gene promoter region will facilitate the elucidation of its transcriptional control by factors secreted during inflammatory responses [10].
• The H4-receptor gene spans more than 21 kbp and contains three exons separated by two large introns (>7 kbp) [10].

Anatomical context of HRH4

• Human skin mast cells express H2 and H4, but not H3 receptors [11].
• A new histamine receptor, HH4R, was cloned from human leukocyte cDNA [12].
• Epithelial cells also expressed H1R, H2R and, to some extent, H4R [1].
• In situ hybridization analysis of a wide survey of mouse tissues showed that mouse AXOR35 mRNA is selectively expressed in hippocampus [13].
• Expression of AXOR35 mRNA in human tissues is highest in peripheral blood mononuclear cells and in tissues likely to contain high concentrations of blood cells, such as bone marrow and lung [13].

Associations of HRH4 with chemical compounds

• CONCLUSIONS: Our data showed that histamine exerts both a proproliferative and a proangiogenic effect via H2/H4 receptor activation [14].
• Treatment with either H2/H4 receptor antagonists or celecoxib prevented these effects [14].
• An H3 agonist, N-alpha-methylhistamine (NAMHA), bound specifically to HH4R, while another H3 agonist, R(-)-alpha-methylhistamine (RAMHA), and the H3 antagonist, thioperamide, competed with this binding [12].
• RAMHA, NAMHA, and imetit inhibited forskolin-induced cAMP accumulation in HH4R-expressing cells [12].
• In functional assays, not only an H3 receptor agonist, R-(alpha)-methylhistamine, but also a H3 receptor antagonist, clobenpropit, and a neuroleptic, clozapine, activated GPRv53-expressing cells [7].

Physical interactions of HRH4

• Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives [15].

Other interactions of HRH4

• These observations indicate that the clone is a distinct histamine receptor from HH3R, and thus is named HH4R [12].
• Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro [16].
• Here we review the known biology associated with the H4 receptor, as well the effects of a highly selective H1 receptor antagonist [17].
• A novel orphan G-protein-coupled receptor named GPRv53 was obtained through a search of the human genomic DNA data base and analyzed by rapid amplification of cDNA ends (RACE) [7].
• GPRv53 possessed the features of biologic amine receptors and had the highest homology with H3 receptor among known G-protein-coupled receptors [7].

Analytical, diagnostic and therapeutic context of HRH4

• Furthermore, only H1, H2, and H4 receptors were detectable by Western blot analysis of HMC-1 cells [11].
• Low expression of HH4R was detected in a wide variety of peripheral tissues by RT-PCR; however, in contrast with HH3R, expression was not detected in the brain [12].
• Molecular cloning and characterization of a new human histamine receptor, HH4R [12].
• The distribution of mRNA encoding SP9144 was restricted to cells of the immune system as determined by quantitative PCR [9].
• The H4-receptor gene have been mapped by radiation hybrid experiments (Gene Bridge 4) on chromosome 18q11.2, between the AFMBB11WH5 and CHLC.GATA85D10 markers [10].

References