Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors.
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.
Reddy
Vemuri B
VB
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Iuga
Aurel O
AO
Shimada
Steve G
SG
LaMotte
Robert H
RH
Lerner
Ethan A
EA
D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D031299:Mucuna / Q000201:enzymology* / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D018514:Plant Structures / Q000201:enzymology / Q000633:toxicity; D011537:Pruritus / Q000139:chemically induced / Q000201:enzymology*; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*
D008024:Ligands; D010936:Plant Extracts; D044462:Receptors, Proteinase-Activated; D003546:Cysteine Endopeptidases