Ishikawa San-E, Saito Tomoyuki, Saito Takako, Kasono Keizo, Funayama Hiroshi
Department of Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan.
Prog Brain Res. 2008;170:581-8. doi: 10.1016/S0079-6123(08)00445-7.
In a state of chronic arginine vasopressin (AVP)-induced antidiuresis, the antidiuretic efficacy has been attenuated: a phenomenon known as "AVP escape". We compared the experimental SIADH rats with 1-deamino-8-D-AVP (dDAVP)-excess rats. The SIADH rats, but not the dDAVP-excess rats, showed a marked attenuation of urinary concentrating ability. This is closely associated with diminished up-regulation of aquaporin-2 (AQP-2) mRNA and protein expression. The following in vitro study clarified tonicity-response elements in the 5'-flanking region of AQP-2 gene. There are at least more than two hypertonicity-response elements, and a hypotonicity-response element resided at tonicity-response enhancer (TonE) (-570 to -560bp) in the AQP-2 gene. Hypotonicity directly reduced the cAMP-induced AQP-2 promoter activity by mediating JNK kinase. Reduction in transcriptional regulation of AQP-2 under hypotonic state may support the in vivo finding of AVP escape phenomenon in chronic AVP-induced antidiuresis.
在慢性精氨酸加压素（AVP）诱导的抗利尿状态下，抗利尿作用减弱：这种现象被称为“AVP逃逸”。我们将实验性抗利尿激素分泌异常综合征（SIADH）大鼠与1-去氨基-8-D-精氨酸加压素（dDAVP）过量大鼠进行了比较。SIADH大鼠而非dDAVP过量大鼠表现出明显的尿浓缩能力减弱。这与水通道蛋白-2（AQP-2）mRNA和蛋白表达上调减弱密切相关。以下体外研究阐明了AQP-2基因5'侧翼区域的渗透压反应元件。AQP-2基因中至少有两个以上的高渗反应元件，且一个低渗反应元件位于渗透压反应增强子（TonE）（-570至-560bp）处。低渗通过介导JNK激酶直接降低cAMP诱导的AQP-2启动子活性。低渗状态下AQP-2转录调控的降低可能支持慢性AVP诱导的抗利尿中AVP逃逸现象的体内发现。
