Involvement of TRPV4 in Serotonin-Evoked Scratching

• Published in: Journal of investigative dermatology Vol. 136; no. 1; pp. 154 - 160
• Main Authors: Akiyama, Tasuku, Ivanov, Margaret, Nagamine, Masaki, Davoodi, Auva, Carstens, Mirela I., Ikoma, Akihiko, Cevikbas, Ferda, Kempkes, Cordula, Buddenkotte, Joerg, Steinhoff, Martin, Carstens, E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2016
• Subjects: Animals; Behavior, Animal - drug effects; Disease Models, Animal; Histamine - adverse effects; Histamine - pharmacology; Immunohistochemistry; Injections, Intradermal; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Pruritus - chemically induced; Pruritus - metabolism; Pruritus - pathology; Random Allocation; Receptor, PAR-2 - drug effects; Receptor, PAR-2 - metabolism; Reference Values; Sensory Receptor Cells - drug effects; Serotonin - adverse effects; Serotonin - pharmacology; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; PAR; TRP; Mrgpr; TRPV4; DRG; TRPV1KO; TRPV1; 5-HT; TRPV4KO; WT
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/JID.2015.388

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.