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

Full Abstract

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.

Author information

Author/s: Yamaura, Katsunori (K); Oda, Manabu (M); Suwa, Eriko (E); Suzuki, Masahiko (M); Sato, Hiromi (H); Ueno, Koichi (K);

Journal and publication information

Publication Type: Letter; Research Support, Non-U.S. Gov't

Journal: The Journal of toxicological sciences (J Toxicol Sci), published in Japan. (Language: eng)

Reference: 2009-Oct; vol 34 (issue 4) : pp 427-31

Dates: Created 2009/08/04; Completed 2009/11/02;

PMID: 19652466, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Disease Models, Animal
Epidermis - metabolism
Histamine
Histamine Antagonists - therapeutic use
Humans
Indoles - therapeutic use
Keratinocytes - metabolism

Male
Mice
Mice, Inbred ICR
Piperazines - therapeutic use
Pruritus - chemically induced; drug therapy
Receptors, G-Protein-Coupled - antagonists & inhibitors; metabolism
Receptors, Histamine - metabolism
Substance P

Associated Chemicals: 1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine (0) ; HRH4 protein, human (0) ; Histamine Antagonists (0) ; Indoles (0) ; Piperazines (0) ; Receptors, G-Protein-Coupled (0) ; Receptors, Histamine (0) ; Substance P (33507-63-0) ; Histamine (51-45-6)

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