Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus

• Published in: Journal of allergy and clinical immunology Vol. 119; no. 1; pp. 176 - 183
• Main Authors: Dunford, Paul J., MSc, Williams, Kacy N., BS, Desai, Pragnya J., MSc, Karlsson, Lars, MD, PhD, McQueen, Daniel, PhD, Thurmond, Robin L., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 2007; Elsevier Limited
• Subjects: Allergies; Allergy and Immunology; Animals; Biological and medical sciences; Bone marrow; Chronic illnesses; Disease Models, Animal; Edema - chemically induced; Experiments; Female; Foot; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histamine; Histamine Agonists - pharmacology; Histamine Antagonists - pharmacology; Hypotheses; Immunopathology; Indoles - pharmacology; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Piperazines - pharmacology; Pruritus - chemically induced; Pruritus - drug therapy; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Receptors, Histamine - deficiency; Receptors, Histamine - genetics; Receptors, Histamine H1 - metabolism; Receptors, Histamine H4; pruritus; Histamine H 4 receptor wild-type; Histamine H 2 receptor; Histamine H 4 receptor knockout; histamine H 4 receptor; mast cells; Histamine H 3 receptor; Histamine; histamine H 1 receptor; H 3R; H 4R; H 1R; H 2R; Immunopathology; Skin disease; Pruritus; Antihistaminic; histamine H4 receptor; Immunology; histamine H1 receptor; Mast cell; Antagonist; H1 Histamine receptor; Biological receptor
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2006.08.034

Background Histamine is a potent mediator of itch in humans, yet histamine H1 receptor antagonists have been shown to be of limited use in the treatment of certain chronic pruritic diseases. The histamine H4 receptor is a recently described histamine receptor, expressed on hematopoietic cells, linked to the pathology of allergy and asthma. Objective The contribution of the novel histamine H4 receptor to histaminergic and allergic pruritus was investigated. Results Histamine and a selective histamine H4 receptor agonist caused scratching responses in mice, which were almost completely attenuated in histamine H4 receptor knockout mice or by pretreatment with the selective histamine H4 receptor antagonist, JNJ 7777120. Pruritus induced by allergic mechanisms was also potently inhibited with histamine H4 receptor antagonist treatment or in histamine H4 receptor knockout mice. In all cases, the inhibitory effect of histamine H4 receptor antagonist was greater than those observed with histamine H1 receptor antagonists. The histamine H4 receptor–mediated pruritus was shown to be independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons. Conclusion These results demonstrate that the histamine H4 receptor is involved in pruritic responses in mice to a greater extent than the histamine H1 receptor. Clinical implications Histamine H4 receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H1 receptor antagonists are not effective.