TY - JOUR
T1 - Involvement of TRPV4 in serotonin-evoked scratching
AU - Akiyama, Tasuku
AU - Ivanov, Margaret
AU - Nagamine, Masaki
AU - Davoodi, Auva
AU - Carstens, Mirela I.
AU - Ikoma, Akihiko
AU - Cevikbas, Ferda
AU - Kempkes, Cordula
AU - Buddenkotte, Joerg
AU - Steinhoff, Martin
AU - Carstens, E.
N1 - Funding Information:
The work was supported by grants from the National Institutes of Health DE013685 (to EEC), AR057194 (to EEC), AR063228 (to TA), AR059402-01 (to MS), and SFI senior investigator award (to MS). The authors thank Dr. Tudor Selescu and Dr. Oliver Bogen for their helpful comments. The TRPV4KO mice were kindly provided by Dr. J. Levine via Dr. N. Bunnett. The original source of the mice was Dr. W. Liedtke. The TRPV1KO mice and the TRPA1KO mice were kindly provided by Dr. D. Julius.
Publisher Copyright:
© 2015 The Authors.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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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U2 - 10.1038/JID.2015.388
DO - 10.1038/JID.2015.388
M3 - Article
C2 - 26763435
AN - SCOPUS:84959471003
VL - 136
SP - 154
EP - 160
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 1
ER -