Involvement of TRPV4 in Serotonin-Evoked Scratching.
Involvement of TRPV4 in Serotonin-Evoked Scratching.
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DOI：
10.1038/jid.2015.388
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Carstens E
中科院分区：
文献类型：
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作者：
Akiyama T;Ivanov M;Nagamine M;Davoodi A;Carstens MI;Ikoma A;Cevikbas F;Kempkes C;Buddenkotte J;Steinhoff M;Carstens E
几种热敏 TRP 通道（TRPV1、-3；TRPA1）与瘙痒有关。相比之下，瞬时感受器电位 4 型香草酸 (TRPV4) 在瘙痒中的作用尚不清楚。因此，我们研究了TRPV4（一种温度敏感的阳离子通道）是否在小鼠急性瘙痒中发挥重要作用。皮内注射四种不同的瘙痒剂，包括血清素（5-羟色胺，5-HT）、组胺、SLIGRL（PAR2/MrgprC11 激动剂）和氯喹（MrgprA3 激动剂），并评估与瘙痒相关的抓挠行为。与野生型 (WT) 小鼠相比，TRPV4 敲除 (TRPV4KO) 小鼠表现出 5-HT 诱发的抓挠次数明显减少。值得注意的是，在 SLIGRL 和组胺引起的抓挠次数方面，TRPV4KO 和 WT 小鼠之间没有观察到差异。 TRPV4 拮抗剂预处理可显着减弱 5-HT 引起的体内抓挠。在培养的原代小鼠背根神经节 (DRG) 神经元中使用钙成像，与 WT 小鼠相比，TRPV4KO 中神经元在应用 5-HT（而非其他瘙痒剂）后的反应明显较低。 TRPV4 拮抗剂显着抑制 WT 小鼠 DRG 细胞中 5-HT 诱发的反应。通过钙成像评估，大约 90% 的 5-HT 敏感 DRG 神经元对 TRPV4 抗体具有免疫反应性。这些结果表明 5-羟色胺引起的瘙痒与 TRPV4 相关。
Several thermo-sensitive TRP channels (TRPV1, -3; TRPA1) 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-hydroxytrytamine, 5-HT), histamine, SLIGRL (PAR2/MrgprC11 agonist) and chloroquine (MrgprA3 agonist) were intradermally injected and itch-related scratching behavior was assessed. TRPV4 knockout (TRPV4KO) mice exhibited significantly fewer 5-HT-evoked scratching bouts compared to wild-type (WT) mice. Notably, no differences between TRPV4KO and WT 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 (DRG) neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4KO compared to WT mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in DRG cells from WT mice. Approximately 90% of 5-HT-sensitive DRG neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that serotonin-induced itch is linked to TRPV4.