The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases.
The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases.
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DOI：
10.3389/fphar.2016.00023
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发表时间：
2016
影响因子：
5.6
通讯作者：
Klussmann E
中科院分区：
文献类型：
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作者：
Vukićević T;Schulz M;Faust D;Klussmann E
精氨酸加压素(AVP)刺激水通道蛋白2(AQP2)从细胞内小泡重新分布到肾集合管主细胞质膜。通过这种AVP，人体肾脏每天产生的170000 L初级尿液中有10%的水被重吸收。该综述讨论了AVP诱导AQP2重新分布的分子机制，特别是对参与其定位控制的蛋白质进行了概述。阻止AQP2插入质膜的缺陷会导致尿崩症。这种疾病可以是后天的，也可以是遗传的，以多尿和多饮为特征。反之亦然，该系统的上调导致AQP2在质膜上的优势定位，导致过度的水分滞留和低钠血症，如抗利尿激素分泌不当综合征(SIADH)、晚期心力衰竭或肝硬变。本文简要总结了目前治疗这种水平衡紊乱的药物疗法，并讨论了新发现的控制AQP2的机制对于开发新的药理策略的价值。水平衡障碍的治疗需要创新的概念，因为由于缺乏因果治疗，有医学上的需要。
Arginine-vasopressin (AVP) stimulates the redistribution of water channels, aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. By this AVP directs 10% of the water reabsorption from the 170 L of primary urine that the human kidneys produce each day. This review discusses molecular mechanisms underlying the AVP-induced redistribution of AQP2; in particular, it provides an overview over the proteins participating in the control of its localization. Defects preventing the insertion of AQP2 into the plasma membrane cause diabetes insipidus. The disease can be acquired or inherited, and is characterized by polyuria and polydipsia. Vice versa, up-regulation of the system causing a predominant localization of AQP2 in the plasma membrane leads to excessive water retention and hyponatremia as in the syndrome of inappropriate antidiuretic hormone secretion (SIADH), late stage heart failure or liver cirrhosis. This article briefly summarizes the currently available pharmacotherapies for the treatment of such water balance disorders, and discusses the value of newly identified mechanisms controlling AQP2 for developing novel pharmacological strategies. Innovative concepts for the therapy of water balance disorders are required as there is a medical need due to the lack of causal treatments.
影响因子：
--
作者：
Heinke F;Labudde D
通讯作者：
Labudde D