期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 686, 期 1-3, 页码 16-21出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.04.024
关键词
Cathepsin E; Endothelin-1; Itch; Keratinocyte; Mast cell; Scratching
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan [22790063, 23390153]
- Health, Labor and Welfare Ministry, Japan
- Grants-in-Aid for Scientific Research [23390153, 22790063] Funding Source: KAKEN
This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ETA receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H-1 histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH2, or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis. (C) 2012 Elsevier B.V. All rights reserved.
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