Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist

Katsunori Yamaura, Manabu Oda, Eriko Suwa, Masahiko Suzuki, Hiromi Sato, Koichi Ueno

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Many medicines exist which can cause pruritus (itching) as "serious adverse events." Many severe pruritic conditions respond poorly to histamine H1 receptor antagonists; there is no generally accepted antipruritic treatment. Recently described histamine H4 receptors are expressed in haematopoietic cells and have been linked to the pathology of allergy and asthma. We previously reported their expression in human dermal fibroblasts; in this study we have investigated H4 receptor expression in human epidermal tissue and found it to be greater in keratinocytes in the epidermal upper layer than in the lower layer. We have also investigated the effect of histamine H4 receptor antagonists on histamine H1 receptor antagonist-resistant pruritus using a mouse model. Scratching behavior was induced by histamine (300 nmol) or substance P (100 nmol) injected intradermally into the rostral part of the back of each mouse. Fexofenadine, a histamine H1 receptor antagonist, reduced scratching induced by histamine but not by substance P, whereas JNJ7777120, a histamine H4 receptor antagonist, significantly reduced both histamine- and substance P-induced scratching. These results suggest that H4 receptor antagonists may be useful for treatment of H1 receptor antagonist-resistant pruritus.

Original languageEnglish
Pages (from-to)427-431
Number of pages5
JournalJournal of Toxicological Sciences
Issue number4
Publication statusPublished - 2009 Aug
Externally publishedYes



  • Histamine H4 receptor
  • JNJ7777120
  • Keratinocytes
  • Pruritus
  • Substance P

ASJC Scopus subject areas

  • Toxicology

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