title: HTR7 Mediates Serotonergic Acute and Chronic Itch.
abstract: Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor HTR7 as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 displayed reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Shannan P
authors.initials: SP
authors.lastname: McClain
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Batia
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Wilson
authors.affiliation: Neurobiology Course, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kienzler
authors.affiliation: Neurobiology Course, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Lyman
authors.affiliation: Neurobiology Course, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
authors.forename: Anne Sofie Braun
authors.initials: AS
authors.lastname: Olsen
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Justin F
authors.initials: JF
authors.lastname: Wong
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Stucky
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: rbrem@buckinstitute.org.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Brem
authors.affiliation: Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: dbautista@berkeley.edu.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Bautista
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000378:metabolism; D008811:Mice, Inbred DBA / Q000235:genetics* / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C104425:serotonin 7 receptor