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

Abstract

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.

• Authors: Kenichiro Tsujii, Tsugunobu Andoh, Haruna Ui, Jung-Bum Lee, Yasushi Kuraishi
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 109 Issue 3 Pg. 388-95 (Mar 2009) ISSN: 1347-8613 [Print] Japan
• PMID: 19270428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamidines
• Guanidines
• Oligopeptides
• Protease Inhibitors
• Receptor, PAR-2
• seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
• Tryptases
• nafamostat

Topics

• Animals
• Benzamidines
• Chronic Disease
• Dermatitis, Atopic (physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epidermal Cells
• Epidermis (metabolism)
• Guanidines (administration & dosage, pharmacology)
• Keratinocytes (metabolism)
• Male
• Mast Cells (metabolism)
• Mice
• Oligopeptides (administration & dosage)
• Protease Inhibitors (administration & dosage, pharmacology)
• Receptor, PAR-2 (metabolism)
• Tryptases (metabolism)