Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

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

Authors: Sarah R Wilson, Kristin A Gerhold, Amber Bifolck-Fisher, Qin Liu, Kush N Patel, Xinzhong Dong, Diana M Bautista

Journal, date & volume: Nat. Neurosci., 2011 May , 14, 595-602

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21460831

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.