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

Abstract

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.

DOI: 10.1038/nn.2789

Extracted Key Phrases

02004002011201220132014201520162017
Citations per Year

1,880 Citations

Semantic Scholar estimates that this publication has 1,880 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Wilson2011TRPA1IR, title={TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch}, author={Sarah R. Wilson and Kristin A. Gerhold and Amber Bifolck-Fisher and Qin Liu and Kush N. Patel and Xinzhong Dong and Diana Bautista}, booktitle={Nature neuroscience}, year={2011} }