Inner ear AVP-V2R-AQP2 signaling pathway is involved in the induction of motion sickness
Inner ear AVP-V2R-AQP2 signaling pathway is involved in the induction of motion sickness
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内耳精氨酸加压素-加压素受体2-水通道蛋白2信号通路参与晕动病的诱发
DOI：
10.1124/jpet.119.264390
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发表时间：
2020
影响因子：
3.5
通讯作者：
Jiang ZL et al.
中科院分区：
文献类型：
--
作者：
Xu LH;Jiang ZL et al.
研究表明，内耳精氨酸加压素（AVP）、加压素受体2（V2R）和水通道蛋白2（AQP2）信号通路通过调节内淋巴平衡，在听力和平衡功能中发挥重要作用；然而，该信号通路对晕动病发生的贡献尚不清楚。本研究旨在探讨内耳AVP-V2R-AQP2信号通路的激活是否与晕动病的诱发有关，以及V2R拮抗剂莫扎瓦普坦是否可以减轻晕动病。我们发现，旋转刺激和腹腔内 AVP 注射都会诱导大鼠条件性味觉厌恶（已证实的晕动病行为指标），并激活 AVP-V2R-AQP2 信号通路，内耳中的 V2R 下调，并且在大鼠内淋巴囊培养的上皮细胞中灌注 AVP 会诱导该通路信号的类似变化。前庭训练、V2R 拮抗剂莫扎瓦普坦或 PKA 抑制剂 H89 减弱了 V2R-AQP2 通路信号传导的这些变化，同时减少了旋转刺激或 DDAVP（一种 V2R 激动剂）引起的大鼠和狗的晕动病。因此，我们的结果表明内耳 AVP-V2R-AQP2 信号通路的激活可能与晕动病的发生有关。因此，针对内耳 AVP V2R 的 mozavaptan 可能为我们提供减少晕动病的新应用选择。意义声明 晕动病影响许多旅行或工作的人。在本研究中，我们的结果表明，内耳精氨酸加压素-加压素受体 2 (V2R)-水通道蛋白 2 信号通路的激活可能与晕动病的发生有关，并且用 V2R 拮抗剂 mozavaptan 阻断 V2R 可以更有效地减少大鼠和狗的晕动病；因此，我们展示了一种引起晕动病的新机制和一种减少晕动病的新候选药物。
It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus– or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.
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DOI：
--
发表时间：
1997-06
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
Y. Matsumura;S. Uchida;T. Rai;S. Sasaki;F. Marumo
通讯作者：
Y. Matsumura;S. Uchida;T. Rai;S. Sasaki;F. Marumo
AVP 通过 V1b 受体调节前庭核可能导致大鼠晕动病的发生
影响因子：
3.6
作者：
Xu LH;Tang GR;Yang JJ;Liu HX;Li JC;Jiang ZL
通讯作者：
Jiang ZL
DOI：
10.1254/jjp.89.324
发表时间：
2002-07-01
期刊：
JAPANESE JOURNAL OF PHARMACOLOGY
影响因子：
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作者：
Ikegaya, Y;Matsuki, N
通讯作者：
Matsuki, N
DOI：
10.1152/ajpregu.00344.2004
发表时间：
2005-02-01
影响因子：
2.8
作者：
Tatewaki, M;Strickland, C;Takahashi, T
通讯作者：
Takahashi, T
DOI：
10.1016/s0163-1047(88)90841-2
发表时间：
1988-09
期刊：
Behavioral and neural biology
影响因子：
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作者：
Richard L. Sutton;Robert A. Fox;N. Daunton
通讯作者：
Richard L. Sutton;Robert A. Fox;N. Daunton