TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.
TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.
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TRPV1 和 PLC 参与组胺 H4 受体诱导的瘙痒。
DOI：
10.1155/2016/1682972
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发表时间：
2016
影响因子：
3.1
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Jian T;Yang N;Yang Y;Zhu C;Yuan X;Yu G;Wang C;Wang Z;Shi H;Tang M;He Q;Lan L;Wu G;Tang Z
组胺H4受体已被证实在引起外周瘙痒中起作用。然而，背根神经节（DRG）神经元上H4受体激活的离子和细胞内信号转导机制仍不清楚。本实验采用细胞培养和钙离子成像技术，研究了DRG神经元H_4受体激活的机制。组胺H_4受体特异性激动剂Immepip dihydrobromide（immepip）经皮肤给药可引起小鼠明显瘙痒。TRPV 1拮抗剂AMG 9810和PLC通路抑制剂U 73122可阻断Immepip诱导的小鼠抓挠行为。应用immepip（8.3-50 μM）也可引起DRG神经元内Ca ~（2+）（[Ca ~（2+）]i）的剂量依赖性增加。我们发现77.8%的immepip致敏的DRG神经元对TRPV 1选择性激动剂辣椒素有反应。U 73122可抑制immepip诱导的Ca ~（2+）反应。此外，immepip诱导的[Ca 2 +]i增加可被钌红、辣椒平和AMG 9810阻断;但不能被TRPA 1拮抗剂HC-030031阻断。这些结果表明，TRPV 1而不是TRPA 1是组胺H4受体下游信号通路中诱导DRG神经元反应的重要离子通道，提示TRPV 1可能通过激活H4受体参与组胺诱导的瘙痒反应机制。
Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)—a histamine H4 receptor special agonist under cutaneous injection—obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3–50 μM) could also induce a dose-dependent increase in intracellular Ca2+ ([Ca2+]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca2+ responses. In addition, immepip-induced [Ca2+]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.