Ecelbarger C A, Nielsen S, Olson B R, Murase T, Baker E A, Knepper M A, Verbalis J G
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1997 Apr 15;99(8):1852-63. doi: 10.1172/JCI119352.
The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.
本研究的目的是调查从血管加压素诱导的抗利尿作用中逃逸是否与任何已知水通道蛋白水通道的调节改变有关。通过渗透微型泵用1-去氨基-[8-D-精氨酸]-血管加压素（dDAVP）进行4天预处理后，将大鼠分为两组：对照组（继续给予dDAVP）和水负荷组（继续给予dDAVP并每日口服水负荷）。在水负荷的第二天，观察到水负荷大鼠的尿量显著增加，表明血管加压素逃逸开始。逃逸的开始在时间上与肾水通道蛋白-2蛋白的显著降低（通过半定量免疫印迹法测量）相吻合，其在第2天开始，到第3天降至对照水平的17%。相比之下，水通道蛋白1、3或4的肾表达没有降低。全肾水通道蛋白-2蛋白的显著抑制伴随着全肾水通道蛋白-2 mRNA水平的相应抑制。免疫细胞化学定位和差速离心研究表明，在血管加压素逃逸期间，水通道蛋白-2向质膜的转运保持完整。结果表明，从血管加压素诱导的抗利尿作用中逃逸至少部分归因于肾集合管中水通道蛋白-2水通道表达的血管加压素非依赖性降低。
