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

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. To determine the mechanism by which these proteases function. The ability of these proteases to activate protease-activated receptors was determined by ratiometric calcium imaging. We show here that bromelain, ficin and papain activate protease-activated receptors 2 and 4. 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.