Abstract
Cowhage is routinely used in human studies of histamine-independent itch. As such, it is of interest to understand its mechanism of action. The active component of cowhage is a cysteine protease called mucunain. As serine proteases can activate members of the protease-activated receptor (PAR) family to induce itch and pain, the mechanism of action of mucunain and cathepsin S, a human cysteine protease, were likewise thought to be through activation of PARs. The demonstration that cathepsin S activates members of the Mas-related G-protein coupled receptor family to induce itch led us to evaluate the activity of mucunain on these receptors. We find that mucunain activates the human receptors MRPGRX1 and MRGPRX2 and induces degranulation of human mast cells. These findings indicate that Mrgprs may be involved in itch induced by cowhage.
Publication types
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Letter
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Degranulation / immunology
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Cysteine Proteases / immunology*
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Cysteine Proteases / metabolism
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HEK293 Cells
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Histamine / immunology
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Histamine / metabolism
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Humans
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Mast Cells / immunology
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Mucuna / chemistry
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Mucuna / immunology*
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Nerve Tissue Proteins / immunology*
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Nerve Tissue Proteins / metabolism
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Plant Proteins / immunology*
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Plant Proteins / metabolism
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Pruritus / immunology*
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Receptors, G-Protein-Coupled / immunology*
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Neuropeptide / immunology*
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Receptors, Neuropeptide / metabolism
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Signal Transduction / immunology
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Skin / cytology
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Skin / immunology
Substances
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MRGPRX2 protein, human
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Nerve Tissue Proteins
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Plant Proteins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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mas-related gene-X1 receptor, human
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Histamine
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Cysteine Proteases