4.7 Article

Involvement of TRPV4 in Serotonin-Evoked Scratching

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JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 136, 期 1, 页码 154-160

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ELSEVIER SCIENCE INC
DOI: 10.1038/JID.2015.388

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资金

  1. National Institutes of Health [DE013685, AR057194, AR063228, AR059402-01]
  2. SFI
  3. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R00AR063228, R01AR057194, R01AR059402, K99AR063228] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE013685] Funding Source: NIH RePORTER

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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.

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