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 PAR_1-4 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 PAR ₁, PAR₂, and PAR₄ are involved in itch and that histamine is a cause of itch related to PAR₁ and PAR₄, but not PAR₂.