title: Involvement of TRPV4 in Serotonin-Evoked Scratching.
abstract: Several thermosensitive transient receptor potential channels (transient receptor potential vanilloid type-1, -3; transient receptor potential cation channel, subfamily A, member 1) have been implicated in itch. In contrast, the role of transient receptor potential vanilloid type-4 (TRPV4) in itch is unknown. Therefore, we investigated if TRPV4, a temperature-sensitive cation channel, plays an important role in acute itch in mice. Four different pruritogens, including serotonin (5-hydroxytryptamine [5-HT]), histamine, SLIGRL (protease-activated receptors 2/mas-related G-protein-coupled receptor C11 agonist), and chloroquine (mas-related G-protein-coupled receptor A3 agonist), were intradermally injected into mice and itch-related scratching behavior was assessed. TRPV4 knockout mice exhibited significantly fewer 5-HT-evoked scratching bouts compared with wild-type mice. Notably, no differences between TRPV4 knockout and wild-type mice were observed in the number of scratch bouts elicited by SLIGRL and histamine. Pretreatment with a TRPV4 antagonist significantly attenuated 5-HT-evoked scratching in vivo. Using calcium imaging in cultured primary murine dorsal root ganglion neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4 knockout compared with wild-type mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in dorsal root ganglion cells from wild-type mice. Approximately 90% of 5-HT-sensitive dorsal root ganglion neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that 5-HT-induced itch is linked to TRPV4.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA; Department of Dermatology, Department of Anatomy & Cell Biology, Temple Itch Center, Temple University, Philadelphia, Pennsylvania, USA. Electronic address: tasuku.akiyama@temple.edu.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Ivanov
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagamine
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA.
authors.forename: Auva
authors.initials: A
authors.lastname: Davoodi
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA.
authors.forename: Mirela I
authors.initials: MI
authors.lastname: Carstens
authors.affiliation: Departments of Dermatology and Surgery, University of California, San Francisco, USA.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ikoma
authors.affiliation: Departments of Dermatology and Surgery, University of California, San Francisco, USA.
authors.forename: Ferda
authors.initials: F
authors.lastname: Cevikbas
authors.affiliation: Departments of Dermatology and Surgery, University of California, San Francisco, USA.
authors.forename: Cordula
authors.initials: C
authors.lastname: Kempkes
authors.affiliation: Departments of Dermatology and Surgery, University of California, San Francisco, USA; U Dept. of Dermatology and UCD Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Buddenkotte
authors.affiliation: Departments of Dermatology and Surgery, University of California, San Francisco, USA; U Dept. of Dermatology and UCD Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland. Electronic address: Martin.steinhoff@ucd.ie.
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA. Electronic address: eecarstens@ucdavis.edu.
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D006632:Histamine / Q000009:adverse effects / Q000494:pharmacology; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011537:Pruritus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D044464:Receptor, PAR-2 / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D011984:Sensory Receptor Cells / Q000187:drug effects; D012701:Serotonin / Q000009:adverse effects / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D044464:Receptor, PAR-2; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D012701:Serotonin; D006632:Histamine