title: Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch.
abstract: Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt(-/-) mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Kush N
authors.initials: KN
authors.lastname: Patel
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Sonya
authors.initials: S
authors.lastname: Meeker
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011537:Pruritus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C529003:Pirt protein, mouse; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D006632:Histamine