Department of Biosciences, Biotechnologies and Pharmacological Sciences, University of Bari, Bari, Italy.
Biol Cell. 2012 Apr;104(4):201-12. doi: 10.1111/boc.201100049. Epub 2012 Jan 26.
The central role of Na+-K+-2Cl- cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and metabolic alkalosis with high prenatal mortality. On the contrary, excessive NKCC2 activity has been linked with inherited hypertension in humans and in rodent models. Interestingly, in animal models of hypertension, NKCC2 upregulation is achieved by post-translational mechanisms underlining the need to analyse the molecular mechanisms involved in the regulation of NKCC2 trafficking and activity to gain insights in the pathogenesis of hypertension.
位于肾脏 Henle 袢升支粗段细胞顶膜的 Na+-K+-2Cl-协同转运蛋白 2（NKCC2）在介导盐重吸收过程中发挥着中心作用，这一观点可以从袢利尿剂的作用得到证实，袢利尿剂是 NKCC2 的药理学抑制剂，也是目前为止最有效的降压药物之一。此外，编码 NKCC2 的基因突变导致 NKCC2 转运体顶膜靶向和功能受损，会引起一种称为 I 型 Bartter 综合征的病理表型，其特征为严重的血容量不足、低钾血症和代谢性碱中毒，围产期死亡率高。相反，NKCC2 的过度激活与人类和啮齿动物模型中的遗传性高血压有关。有趣的是，在高血压动物模型中，NKCC2 的上调是通过翻译后机制实现的，这强调了需要分析参与 NKCC2 运输和活性调节的分子机制，以深入了解高血压的发病机制。
