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The Journal of Neuroscience, April 23, 2008, 28(17):4331-4335; doi:10.1523/JNEUROSCI.0716-08.2008

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Brief Communications
Cowhage-Evoked Itch Is Mediated by a Novel Cysteine Protease: A Ligand of Protease-Activated Receptors

Vemuri B. Reddy,¹ Aurel O. Iuga,¹ Steve G. Shimada,² Robert H. LaMotte,² and Ethan A. Lerner¹

¹Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, and ²Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence should be addressed to Ethan A. Lerner, Cutaneous Biology Research Center, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129. Email: elerner{at}partners.org

Cowhage spicules provide an important model for histamine-independent itch. We determined that the active component of cowhage, termed mucunain, is a novel cysteine protease. We isolated mucunain and demonstrate that both native and recombinant mucunain evoke the same quality of itch in humans. We also show that mucunain is a ligand for protease-activated receptors two and four. These results support and expand the relationship between proteases, protease-activated receptors, and itch.

Key words: pruritus; cowhage; Mucuna pruriens; cysteine protease; protease-activated receptor; receptor

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Received Feb. 15, 2008; revised March 13, 2008; accepted March 17, 2008.

Correspondence should be addressed to Ethan A. Lerner, Cutaneous Biology Research Center, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129. Email: elerner{at}partners.org

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