Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis.
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.
Tsujii
Kenichiro
K
Department of Applied Pharmacology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Japan.
Andoh
Tsugunobu
T
Ui
Haruna
H
Lee
Jung-Bum
JB
Kuraishi
Yasushi
Y
D000818:Animals; D001550:Benzamidines; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000378:metabolism*; D053802:Tryptases / Q000378:metabolism*
D001550:Benzamidines; D006146:Guanidines; D009842:Oligopeptides; D011480:Protease Inhibitors; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D053802:Tryptases; C032855:nafamostat