Department of Otolaryngology, Osaka University, School of Medicine, Suita-city, Osaka, Japan.
J Neuroendocrinol. 2010 Nov;22(11):1157-64. doi: 10.1111/j.1365-2826.2010.02060.x.
Meniere's disease, characterised by episodic vertigo, fluctuating hearing loss and tinnitus, can occur under conditions of stress. Its pathology was first revealed to be inner ear hydrops through temporal bone studies in 1938. Although its pathogenesis has been proposed to be a disorder of water transport in the inner ear, subsequently, it remains unsolved, until now. A recent study revealed that both plasma stress hormone, vasopressin (pAVP) and its receptor, V2 (V2R) expression in the inner ear endolymphatic sac were significantly higher in Meniere's patients. In the present study, to link V2R-related molecules and inner ear hydrops, we examined V2R-linked water channel molecule, aquaporin-2 (AQP2) expression and translocation in human endolymphatic sac. AQP2 mRNA expression in the endolymphatic sac was significantly higher in Meniere's patients by using real-time polymerase chain reaction, as further confirmed by western blotting. AQP2-like immunoreactivity (-LIR) was translocated from luminal to basolateral side with endosomal trapping in the endolymphatic sac at the time of AVP exposure in human endolymphatic sac tissue culture. The similar AQP2-LIR translocation was also demonstrated by forskolin and blocked by vasopressin/V2R specific antagonist, OPC31260 and protein kinase A (PKA) specific antagonists, H-89 and KT-5720. We concluded that in the pathogenesis of inner ear hydrops resulting in Meniere's attacks, pAVP elevation as a result of stress and subsequent V2R-cAMP-PKA-AQP2 activation and endosomal trapping of AQP2 in the endolymphatic sac, might be important as a basis of this disease. Further experimental and clinical studies are needed to better clarify the neuroscientific relationship between stress and Meniere's disease.
梅尼埃病的特征是间歇性眩晕、波动性听力损失和耳鸣，可在应激条件下发生。1938 年通过颞骨研究首次揭示其病理学为内耳积水。尽管其发病机制被提出为内耳水转运紊乱，但此后一直未得到解决，直到现在。最近的一项研究表明，梅尼埃病患者的血浆应激激素血管加压素（pAVP）及其在内耳内淋巴囊的受体 V2（V2R）表达均显著升高。在本研究中，为了将 V2R 相关分子与内耳积水联系起来，我们检查了人类内淋巴囊中的 V2R 相关水通道分子水通道蛋白-2（AQP2）的表达和转位。通过实时聚合酶链反应，发现梅尼埃病患者内淋巴囊中 AQP2 mRNA 表达显著升高，进一步通过 Western blot 证实。在人类内淋巴囊组织培养中，AQP2 样免疫反应性（-LIR）在 AVP 暴露时从腔侧易位到基底外侧侧，并在内淋巴囊中被内体捕获。在福司可林和血管加压素/V2R 特异性拮抗剂 OPC31260 和蛋白激酶 A（PKA）特异性拮抗剂 H-89 和 KT-5720 阻断后，也证明了类似的 AQP2-LIR 易位。我们得出结论，在导致梅尼埃病发作的内耳积水发病机制中，应激导致的 pAVP 升高以及随后的 V2R-cAMP-PKA-AQP2 激活和内淋巴囊中 AQP2 的内体捕获，可能是该病的重要基础。需要进一步的实验和临床研究来更好地阐明应激与梅尼埃病之间的神经科学关系。
