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Publication : TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch.

First Author  Wilson SR Year  2011
Journal  Nat Neurosci Volume  14
Issue  5 Pages  595-602
PubMed ID  21460831 Mgi Jnum  J:172290
Mgi Id  MGI:5006882 Doi  10.1038/nn.2789
Citation  Wilson SR, et al. (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14(5):595-602
abstractText  Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. In many cases, pathological itch is insensitive to antihistamine treatment. Recent studies have identified members of the Mas-related G protein-coupled receptor (Mrgpr) family that are activated by mast cell mediators and promote histamine-independent itch. MrgprA3 and MrgprC11 act as receptors for the pruritogens chloroquine and BAM8-22, respectively. However, the signaling pathways and transduction channels activated downstream of these pruritogens are largely unknown. We found that TRPA1 is the downstream target of both MrgprA3 and MrgprC11 in cultured sensory neurons and heterologous cells. TRPA1 is required for Mrgpr-mediated signaling, as sensory neurons from TRPA1-deficient mice exhibited markedly diminished responses to chloroquine and BAM8-22. Similarly, TRPA1-deficient mice displayed little to no scratching in response to these pruritogens. Our findings indicate that TRPA1 is an essential component of the signaling pathways that promote histamine-independent itch.
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