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Gene Review

HRH4  -  histamine receptor H4

Homo sapiens

Synonyms: AXOR35, BG26, G-protein coupled receptor 105, GPCR105, GPRv53, ...
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Disease relevance of HRH4


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


Anatomical context of HRH4


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


Other interactions of HRH4


Analytical, diagnostic and therapeutic context of HRH4


  1. Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Sander, L.E., Lorentz, A., Sellge, G., Coëffier, M., Neipp, M., Veres, T., Frieling, T., Meier, P.N., Manns, M.P., Bischoff, S.C. Gut (2006) [Pubmed]
  2. Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats. Adachi, N., Liu, K., Motoki, A., Nishibori, M., Arai, T. Eur. J. Pharmacol. (2006) [Pubmed]
  3. The use of IRES-based bicistronic vectors allows the stable expression of recombinant G-protein coupled receptors such as NPY5 and histamine 4. Allera-Moreau, C., Chomarat, P., Audinot, V., Cogé, F., Gillard, M., Martineau, Y., Boutin, J.A., Prats, A.C. Biochimie (2006) [Pubmed]
  4. The histamine H4 receptor in autoimmune disease. Zhang, M., Venable, J.D., Thurmond, R.L. Expert opinion on investigational drugs. (2006) [Pubmed]
  5. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. Gutzmer, R., Diestel, C., Mommert, S., Köther, B., Stark, H., Wittmann, M., Werfel, T. J. Immunol. (2005) [Pubmed]
  6. Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70. Johnson, C.A., White, D.A., Lavender, J.S., O'Neill, L.P., Turner, B.M. J. Biol. Chem. (2002) [Pubmed]
  7. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. Oda, T., Morikawa, N., Saito, Y., Masuho, Y., Matsumoto, S. J. Biol. Chem. (2000) [Pubmed]
  8. Discovery of a novel member of the histamine receptor family. Nguyen, T., Shapiro, D.A., George, S.R., Setola, V., Lee, D.K., Cheng, R., Rauser, L., Lee, S.P., Lynch, K.R., Roth, B.L., O'Dowd, B.F. Mol. Pharmacol. (2001) [Pubmed]
  9. Cloning and characterization of a novel human histamine receptor. Morse, K.L., Behan, J., Laz, T.M., West, R.E., Greenfeder, S.A., Anthes, J.C., Umland, S., Wan, Y., Hipkin, R.W., Gonsiorek, W., Shin, N., Gustafson, E.L., Qiao, X., Wang, S., Hedrick, J.A., Greene, J., Bayne, M., Monsma, F.J. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  10. Structure and expression of the human histamine H4-receptor gene. Cogé, F., Guénin, S.P., Rique, H., Boutin, J.A., Galizzi, J.P. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  11. Human skin mast cells express H2 and H4, but not H3 receptors. Lippert, U., Artuc, M., Grützkau, A., Babina, M., Guhl, S., Haase, I., Blaschke, V., Zachmann, K., Knosalla, M., Middel, P., Krüger-Krasagakis, S., Henz, B.M. J. Invest. Dermatol. (2004) [Pubmed]
  12. Molecular cloning and characterization of a new human histamine receptor, HH4R. Nakamura, T., Itadani, H., Hidaka, Y., Ohta, M., Tanaka, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  13. Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Zhu, Y., Michalovich, D., Wu, H., Tan, K.B., Dytko, G.M., Mannan, I.J., Boyce, R., Alston, J., Tierney, L.A., Li, X., Herrity, N.C., Vawter, L., Sarau, H.M., Ames, R.S., Davenport, C.M., Hieble, J.P., Wilson, S., Bergsma, D.J., Fitzgerald, L.R. Mol. Pharmacol. (2001) [Pubmed]
  14. The role of cyclooxygenase-2 in mediating the effects of histamine on cell proliferation and vascular endothelial growth factor production in colorectal cancer. Cianchi, F., Cortesini, C., Schiavone, N., Perna, F., Magnelli, L., Fanti, E., Bani, D., Messerini, L., Fabbroni, V., Perigli, G., Capaccioli, S., Masini, E. Clin. Cancer Res. (2005) [Pubmed]
  15. Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. Smits, R.A., Lim, H.D., Stegink, B., Bakker, R.A., de Esch, I.J., Leurs, R. J. Med. Chem. (2006) [Pubmed]
  16. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes. Neuhaus, J., Weimann, A., Stolzenburg, J.U., Dawood, W., Schwalenberg, T., Dorschner, W. World journal of urology. (2006) [Pubmed]
  17. Histamine H4 receptor antagonists: the new antihistamines? Fung-Leung, W.P., Thurmond, R.L., Ling, P., Karlsson, L. Current opinion in investigational drugs (London, England : 2000) (2004) [Pubmed]
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