期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 109, 期 3, 页码 388-395出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08332FP
关键词
atopic dermatitis; itch; scratching; tryptase; proteinase-activated receptor
资金
- KAKENHI [19390020, 19790051]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Research Foundation for Pharmaceutical Sciences
- Grants-in-Aid for Scientific Research [19790051, 19390020] Funding Source: KAKEN
This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1-10 mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR(2) antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR(2)-activating peptide SLI-GRL-NH2 but not PAR(1), (3), (4)-activating peptides, elicited scratching at doses of 10 - 100 nmol/site in healthy mice. PAR(2)-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR(2) and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.
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