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J. Invest. Dermatol. · Jan 2016
Comparative StudyInvolvement of TRPV4 in Serotonin-Evoked Scratching.
- Tasuku Akiyama, Margaret Ivanov, Masaki Nagamine, Auva Davoodi, Mirela I Carstens, Akihiko Ikoma, Ferda Cevikbas, Cordula Kempkes, Joerg Buddenkotte, Martin Steinhoff, and E Carstens.
- 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.
- J. Invest. Dermatol. 2016 Jan 1; 136 (1): 154-60.
AbstractSeveral 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.Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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