Skip to main content

Advertisement

SpringerLink
Log in

The new biology of histamine receptors

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

The physiologic functions of histamine have been recognized for more than 100 years, yet new roles are still being uncovered. Most importantly, a newly discovered receptor of the amine has helped refine our understanding of histamine. This new receptor, the histamine H4 receptor (H4R), has a higher affinity for histamine compared with the histamine H1 receptor and appears to be more selectively expressed, found mainly on hematopoietic cells. H4R is involved in chemotaxis and inflammatory mediator release by eosinophils, mast cells, monocytes, dendritic cells, and T cells. Studies in animal models using selective antagonists or H4R-deficient mice have shown a role for the receptor in inflammation in vivo. In particular, H4R antagonists have shown promise in experimental models of asthma and pruritus, two conditions where currently marketed antihistamines targeting the histamine H1 receptor are not optimally effective in humans. Thus, a new class of H4R-specific antihistamines may be distinctively effective in treating allergic diseases associated with chronic pruritus and asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Adlesic M, Verdrengh M, Bokarewa M, et al.: Histamine in rheumatoid arthritis. Scand J Immunol 2007, 65:530–537.

    Article  PubMed  CAS  Google Scholar 

  2. Leurs R, Bakker RA, Timmerman H, de Esch IJP: The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov 2005, 4:107–120.

    Article  PubMed  CAS  Google Scholar 

  3. Gantner F, Sakai K, Tusche MW, et al.: Histamine H4 and H2 receptors control histamine-induced interleukin-16 release from human CD8+ T cells. J Pharmacol Exp Ther 2002, 303:300–307.

    Article  PubMed  CAS  Google Scholar 

  4. Ling P, Ngo K, Nguyen S, et al.: Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004, 142:161–171.

    Article  PubMed  CAS  Google Scholar 

  5. Dijkstra D, Leurs R, Chazot P, et al.: Histamine downregulates monocyte CCL2 production through the histamine H4 receptor. J Allergy Clin Immunol 2007, 120:300–307.

    Article  PubMed  CAS  Google Scholar 

  6. Sander LE, Lorentz A, Sellge G, et al.: Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Gut 2006, 55:498–504.

    Article  PubMed  CAS  Google Scholar 

  7. Coge F, Guenin SP, Rique H, et al.: Structure and expression of the human histamine H4-receptor gene. Biochem Biophys Res Commun 2001, 284:301–309.

    Article  PubMed  CAS  Google Scholar 

  8. Nakaya M, Takeuchi N, Kondo K: Immunohistochemical localization of histamine receptor subtypes in human inferior turbinates. Ann Otol Rhinol Laryngol 2004, 113:552–557.

    PubMed  Google Scholar 

  9. Breunig E, Michel K, Zeller F, et al.: Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. J Physiol 2007, 583(Pt 2):731–742.

    Article  PubMed  Google Scholar 

  10. Liu C, Ma X-J, Jiang X, et al.: Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow. Mol Pharmacol 2001, 59:420–426.

    PubMed  CAS  Google Scholar 

  11. Venable JD, Thurmond RL: Development and chemistry of histamine H4 receptor ligands as potential modulators of inflammatory and allergic responses. Anti-Inflammatory Anti-Allergy Agents Med Chem 2006, 5:307–322.

    CAS  Google Scholar 

  12. Lim HD, van Rijn RM, Ling P, et al.: Evaluation of histamine H1-, 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, 314:1310–1321.

    Article  PubMed  CAS  Google Scholar 

  13. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung W-P: Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther 2003, 305:1212–1221.

    Article  PubMed  CAS  Google Scholar 

  14. Thurmond RL, Desai PJ, Dunford PJ, et al.: A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther 2004, 309:404–413.

    Article  PubMed  CAS  Google Scholar 

  15. Fokkens WJ, Godthelp T, Holm AF, et al.: Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non-allergic controls: a biopsy study. Clin Exp Allergy 1992, 22:701–710.

    Article  PubMed  CAS  Google Scholar 

  16. Slater A, Smallman LA, Drake-Lee AB: Increase in epithelial mast cell numbers in the nasal mucosa of patients with perennial allergic rhinitis. J Laryngol Otol 1996, 110:929–933.

    Article  PubMed  CAS  Google Scholar 

  17. Godot V, Arock M, Garcia G, et al.: H(4) histamine receptor mediates optimal migration of mast cell precursors to CXCL12. J Allergy Clin Immunol 2007, 120:827–834.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. O’Reilly M, Alpert R, Jenkinson S, et al.: Identification of a histamine H4 receptor on human eosinophils—role in eosinophil chemotaxis. J Recept Signal Transduction 2002, 22:431–448.

    Article  CAS  Google Scholar 

  20. Gutzmer R, Diestel C, Mommert S, et al.: Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 2005, 174:5224–5232.

    PubMed  CAS  Google Scholar 

  21. Bryce PJ, Mathias CB, Harrison KL, et al.: The H1 histamine receptor regulates allergic lung responses. J Clin Invest 2006, 116:1624–1632.

    Article  PubMed  CAS  Google Scholar 

  22. Morgan RK, McAllister B, Cross L, et al.: Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J Immunol 2007, 178:8081–8089.

    PubMed  CAS  Google Scholar 

  23. Dunford PJ, O’Donnell N, Riley JP, et al.: The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 2006, 176:7062–7070.

    PubMed  CAS  Google Scholar 

  24. Coruzzi G, Adami M, Guaita E, et al.: Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation. Eur J Pharmacol 2007, 563:240–244.

    Article  PubMed  CAS  Google Scholar 

  25. Takeshita K, Sakai K, Bacon KB, Gantner F: Critical role of histamine H4 receptor in leukotriene B4 production and mast cell-dependent neutrophil recruitment induced by zymosan in vivo. J Pharmacol Exp Ther 2003, 307:1072–1078.

    Article  PubMed  CAS  Google Scholar 

  26. Ajuebor MN, Das AM, Virag L, et al.: Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. J Immunol 1999, 162:1685–1691.

    PubMed  CAS  Google Scholar 

  27. Rao NL, Dunford PJ, Xue X, et al.: Anti-inflammatory activity of a potent, selective leukotriene A4 hydrolase inhibitor in comparison with the 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther 2007, 321:1154–1160.

    Article  PubMed  CAS  Google Scholar 

  28. Varga C, Horvath K, Berko A, et al.: Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. Eur J Pharmacol 2005, 522:130–138.

    PubMed  CAS  Google Scholar 

  29. Jarjour N, Calhoun W, Schwartz L, Busse W: Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction. Am Rev Respir Dis 1991, 144:83–87.

    PubMed  CAS  Google Scholar 

  30. Takeda K, Hamelmann E, Joetham A, et al.: Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J Exp Med 1997, 186:449–454.

    Article  PubMed  CAS  Google Scholar 

  31. Paus R, Schmelz M, Biro T, Steinhoff M: Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Investig 2006, 116:1174–1185.

    Article  PubMed  CAS  Google Scholar 

  32. Klein PA, Clark RAF: An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 1999, 135:1522–1525.

    Article  PubMed  CAS  Google Scholar 

  33. Bell JK, McQueen DS, Rees JL: Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in BalbC mice. Br J Pharmacol 2004, 142:374–380.

    Article  PubMed  CAS  Google Scholar 

  34. Dunford PJ, Williams KN, Desai PJ, et al.: Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol 2007, 119:176–183.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Johnson & Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA, 92121, USA

    Robin L. Thurmond

Authors
  1. Jing-Feng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robin L. Thurmond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robin L. Thurmond.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, JF., Thurmond, R.L. The new biology of histamine receptors. Curr Allergy Asthma Rep 8, 21–27 (2008). https://doi.org/10.1007/s11882-008-0005-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-008-0005-y

Keywords

Search

Navigation