title: 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.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
authors: Sarah R
authors: SR
authors: Wilson
authors: Kristin A
authors: KA
authors: Gerhold
authors: Amber
authors: A
authors: Bifolck-Fisher
authors: Qin
authors: Q
authors: Liu
authors: Kush N
authors: KN
authors: Patel
authors: Xinzhong
authors: X
authors: Dong
authors: Diana M
authors: DM
authors: Bautista
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D018501:Antirheumatic Agents; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine; D004195:Disease Models, Animal; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000009:adverse effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009149:Mustard Plant; D009447:Neuroblastoma / Q000473:pathology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010938:Plant Oils / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000074025:TRPA1 Cation Channel; D013997:Time Factors; D014162:Transfection / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; D002118:Calcium; D002211:Capsaicin; D002738:Chloroquine; D004791:Enzyme Inhibitors; D006632:Histamine; D010455:Peptides; D010938:Plant Oils; D043562:Receptors, G-Protein-Coupled; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C470192:Mrgprx1 protein, mouse; C546475:MrgprA3 protein, mouse; C475685:Trpa1 protein, mouse; C027793:mustard oil