Human histamine H4 receptor

Jablonowski JA, Grice CA, Chai W, et al. The first potent and selective non-imidazole human histamine H4 receptor antagonist. / Med Chem 2003 46 3957-60. 

Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R. Evaluation of histamine HI-, H2-, and H3-receptor ligands at the human histamine H4 receptor identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 2005 314 1310-21. 

Kiss, R., Kiss, B., Kdnczdl, A., Szalai, F., Jelinek, 1., Laszlo, V., Noszal, B., Falus, A., and Keresii, G.M. (2008) Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. Journal of Medicinal Chemistry, 51, 3145-3153. 

O Reilly M, Alpert R, Jenkinson S, Gladue RP, Foo S, Trim S, Peter B, Trevethick M, Fidock M Identification of a histamine H4 receptor on human eosinophils - role in eosinophil chemotaxis. J Recept Signal Transduct Res 2002 22 431-448. 

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

Buckland KF, Williams TJ, Conroy DM Histamine induces cytoskeletal changes in human eosinophils via the H4 receptor. Br J Pharmacol 2003 140 1117-1127. 

Gantner F, Sakai K, Tusche MW, Cruikshank WW, Center DM, Bacon KB Histamine h4 and h2 receptors control histamine-induced interleukin-16 release from human CD8+ T cells. J Pharmacol Exp Ther 2002 303 300-307. 

Medina, V., Croci, M., Crescenti, E., Mohamad, N., Sanchez-Jimenez, F., Massari, N., Nunez, M., Cricco, G., Martin, G., Bergoc, R., and Rivera, E. (2008). The role of histamine in human mammary carcinogenesis H3 and H4 receptors as potential therapeutic targets for breast cancer treatment. Cancer Biol. Ther. 7(1), 28-35. 

Histamine is in mast cells, basophils, and platelets. Human skin mast cells express H H2, and H4 receptors, but not H3 receptors. Hi and H2 receptors are involved in wheal formation and erythema, whereas only Hi-receptor agonists cause pruritus. Complete blockade of Hi-receptors does not totally relieve itching, and combinations of Hi and H2 blockers may be superior to H, blockers alone. 

As work on the H4 receptor progresses, evidence is accumulating for an immunomodulating role for histamine in the immune response, and there is much optimism that further insights into the role of H, receptors in immune and inflammatory disorders will yield novel therapeutic agents for the alleviation of a range of allergic conditions. Other demonstrations of the expression of functional histamine receptors on human T and dendritic cells also point to an immunomodulatory effect of histamine. 

Damaj BB, Becerra CB, Esber HJ, Wen Y, Maghazachi AA Functional expression of H4 histamine receptor in human natural Idller cells, monocytes, and dendritic cells. J Immunol 2007 179 7907-7915. 

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