title: Involvement of serine protease and proteinase-activated receptor 2 in dermatophyte-associated itch in mice.
abstract: We investigated the involvement of serine protease and proteinase-activated receptor 2 (PAR(2)) 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 PAR(2) receptor antagonist FSLLRY-NH(2). ADV extract-induced scratching was not inhibited by the H(1) 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 PAR(2) 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 PAR(2) receptor. The present results suggest that serine protease secreted by dermatophytes causes itching through activation of the PAR(2) receptors, which may be a causal mechanism of dernatophytosis itch.
authors: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Tsugunobu
authors: T
authors: Andoh
authors: Yusuke
authors: Y
authors: Takayama
authors: Takako
authors: T
authors: Yamakoshi
authors: Jung-Bum
authors: JB
authors: Lee
authors: Ayako
authors: A
authors: Sano
authors: Tadamichi
authors: T
authors: Shimizu
authors: Yasushi
authors: Y
authors: Kuraishi
mesh_terms: D000818:Animals; D003883:Arthrodermataceae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D011537:Pruritus / Q000201:enzymology*; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D057057:Serine Proteases / Q000502:physiology*
chemical_list: C508716:H-Phe-Ser-Leu-Leu-Arg-Tyr-NH2; D009842:Oligopeptides; D044464:Receptor, PAR-2; D057057:Serine Proteases