Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Journal of Pharmacological Sciences

Jung-Bum Lee²  Tsugunobu Andoh¹  Yasushi Kuraishi¹  Haruna Ui¹  Kenichiro Tsujii¹ 

[1] Department of Applied Pharmacology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Japan;Department of Pharmacognosy, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Japan

关键词: atopic dermatitis;    itch;    scratching;    tryptase;    proteinase-activated receptor;   

DOI  :  10.1254/jphs.08332FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(27)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-PAR2 antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR2-activating peptide SLIGRL-NH2, but not PAR1, 3, 4-activating peptides, elicited scratching at doses of 10 – 100 nmol/site in healthy mice. PAR2-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR2 and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.

【 授权许可】

Unknown