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J Pharmacol Sci. 2009 Mar;109(3):388-95. Epub 2009 Mar 7.

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

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Department of Applied Pharmacology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Japan.


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 SLIGRL-NH(2), 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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