Plant cysteine proteases that evoke itch activate protease-activated receptors.

BACKGROUND: Bromelain, ficin and papain are cysteine proteases from plants that produce itch upon injection into skin. Their mechanism of action has not been considered previously. OBJECTIVES: To determine the mechanism by which these proteases function. METHODS: The ability of these proteases to activate protease-activated receptors was determined by ratiometric calcium imaging. RESULTS: We show here that bromelain, ficin and papain activate protease-activated receptors 2 and 4. CONCLUSIONS: Bromelain, ficin and papain function as signalling molecules and activate protease-activated receptors. Activation of these receptors is the likely mechanism by which these proteases evoke itch.