RT Journal Article
SR Electronic
T1 Involvement of Serine Protease and Proteinase-Activated Receptor 2 in Dermatophyte-Associated Itch in Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 91
OP 96
DO 10.1124/jpet.112.195222
VO 343
IS 1
A1 Tsugunobu Andoh
A1 Yusuke Takayama
A1 Takako Yamakoshi
A1 Jung-Bum Lee
A1 Ayako Sano
A1 Tadamichi Shimizu
A1 Yasushi Kuraishi
YR 2012
UL http://jpet.aspetjournals.org/content/343/1/91.abstract
AB We investigated the involvement of serine protease and proteinase-activated receptor 2 (PAR2) in dermatophyte-induced itch in mice. An intradermal injection of an extract of the dermatophyte Arthroderma vanbreuseghemii (ADV) induced hind-paw scratching, an itch-related behavior. ADV extract-induced scratching was inhibited by the opioid receptor antagonists naloxone and naltrexone, the serine protease inhibitor nafamostat mesylate, and the PAR2 receptor antagonist FSLLRY-NH2. ADV extract-induced scratching was not inhibited by the H1 histamine receptor antagonist terfenadine or by mast cell deficiency. Heat pretreatment of the ADV extract markedly reduced the scratch-inducing and serine protease activities. Proteolytic cleavage within the extracellular N terminus of the PAR2 receptor exposes a sequence that serves as a tethered ligand for the receptor. The ADV extract as well as tryptase and trypsin cleaved a synthetic N-terminal peptide of the PAR2 receptor. The present results suggest that serine protease secreted by dermatophytes causes itching through activation of the PAR2 receptors, which may be a causal mechanism of dernatophytosis itch.