Expression and translocation of aquaporin-2 in the endolymphatic sac in patients with Meniere's disease.
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.
Maekawa
C
C
Department of Otolaryngology, Osaka University, School of Medicine, Suita-city, Osaka, Japan.
Kitahara
T
T
Kizawa
K
K
Okazaki
S
S
Kamakura
T
T
Horii
A
A
Imai
T
T
Doi
K
K
Inohara
H
H
Kiyama
H
H
D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2 / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D004712:Endolymphatic Sac / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008575:Meniere Disease / Q000235:genetics* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009924:Organ Culture Techniques; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D017483:Receptors, Vasopressin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048348:Reverse Transcription / Q000235:genetics; D014178:Translocation, Genetic
D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D012313:RNA; D004247:DNA