Agarwal S K, Gupta A
Department of Nephrology, All India Institute of Medical Sciences, New Delhi - 110 029, India.
Indian J Nephrol. 2008 Jul;18(3):95-100. doi: 10.4103/0971-4065.43687.
Water is the most abundant molecule in any cell. Specialized membrane channel, proteins called aquaporins, facilitate water transport across cell membranes. At least seven aquaporins (AQP): 1, 2, 3, 4, 6, 7, and 11 are expressed in the kidneys. Aquaporins play a role in both the short-term and long-term regulation of water balance as well as in the pathophysiology of water balance disorders. Aquaporin is composed of a single peptide chain consisting of approximately 270 amino acids. Inherited central and nephrogenic diabetes insipidus are primarily due to the decreased expression of AQP2 while mutation in the AQP2 molecule is responsible for inherited central diabetes insipidus. In acquired causes of nephrogenic diabetes insipidus, there is a downregulation of AQP2 expression in the inner medulla of the kidney. Nephrotic syndrome is characterized by excessive sodium and water reabsorption, although in spite of this, patients do not develop hyponatremia. There is a marked downregulation of both AQP2 and AQP3 expression, which could be a physiologic response to extracellular water reabsorption in patients with nephrotic syndrome. There are some conditions in which aquaporin expression has been found to increase such as experimentally induced heart failure, cirrhosis, and pregnancy. Some drugs such as cisplatin and cyclosporine, also alter the expression of aquaporins. The three-pore model of peritoneal transport depicts the importance of aquaporins. Thus, the understanding of renal water channels has solved the mystery behind many water balance disorders. Further insights into the molecular structure and biology of aquaporins will help to lay a foundation for the development of future drugs.
水是任何细胞中含量最丰富的分子。专门的膜通道,即称为水通道蛋白的蛋白质,促进水跨细胞膜的运输。至少七种水通道蛋白(AQP):1、2、3、4、6、7和11在肾脏中表达。水通道蛋白在水平衡的短期和长期调节以及水平衡紊乱的病理生理学中都发挥作用。水通道蛋白由一条由大约270个氨基酸组成的单肽链构成。遗传性中枢性和肾性尿崩症主要是由于AQP2表达降低,而AQP2分子的突变则导致遗传性中枢性尿崩症。在获得性肾性尿崩症的病因中,肾脏内髓质中AQP2的表达下调。肾病综合征的特征是钠和水重吸收过多,尽管如此,患者并不会发生低钠血症。AQP2和AQP3的表达均明显下调,这可能是肾病综合征患者对细胞外水重吸收的一种生理反应。在一些情况下,如实验性诱导的心力衰竭、肝硬化和妊娠,已发现水通道蛋白表达增加。一些药物,如顺铂和环孢素,也会改变水通道蛋白的表达。腹膜转运的三孔模型描述了水通道蛋白的重要性。因此,对肾水通道的认识解开了许多水平衡紊乱背后的谜团。对水通道蛋白分子结构和生物学的进一步深入了解将有助于为未来药物的开发奠定基础。