Activation of proteinase-activated receptors induces itch-associated response through histamine-dependent and -independent pathways in mice.

Proteinase-activated receptor-2 (PAR2) participates in itch, but the role of the other subtypes of this receptor remain unknown. To investigate this issue, scratching, an itch-related behavior, was observed following intradermal injections of the activating peptides of PAR1-4 in mice. Activating peptides of PAR1, PAR2, and PAR4, but not PAR3, induced scratching. The antihistamine terfenadine suppressed scratching elicited by activating peptides of PAR1 and PAR4, but not PAR2. These results suggest that PAR1, PAR2, and PAR4 are involved in itch and that histamine is a cause of itch related to PAR1 and PAR4, but not PAR2.