Laski M E, Pressley T A
Combined Program in Nephrology and Renal Physiology, Texas Tech University Health Sciences Center, Lubbock, USA.
Semin Nephrol. 1999 Nov;19(6):533-50.
Within the past decade an entire family of membrane proteins--aquaporins--which function as transmembrane water channels has been identified; they occur throughout the plant, animal, and bacterial kingdoms. Several family members permit glycerol and urea permeability. Most aquaporins are inhibited by mercury. Constitutively expressed aquaporin 1 is the major permeability channel of the proximal tubule, descending thin limb of the loop of Henle, and it is also found in vasa recta. Aquaporin 2 is expressed in the principal cells of the collecting duct where it shuttles between intracellular vesicles and the apical membrane in response to vasopressin. Aquaporin 2 mutations cause nephrogenic diabetes insipidus; increased aquaporin 2 activity is implicated in the pathophysiology of heart failure, cirrhosis, and nephrotic syndrome. Aquaporins 3 and 4 provide basolateral membrane water channels in the collecting duct. These 4 channels and 6 others are also found elsewhere throughout the body. The physiological importance of several of the channels remains unknown. Aquaporin 1 inhibitors might induce useful diuresis, but humans who lack aquaporin 1 have no significant clinical disease. Inhibition of aquaporin 2 activity by vasopressin receptor antagonists may be useful in heart failure, cirrhosis, nephrotic syndrome, and the syndrome of inappropriate antidiuretic hormone (ADH) release.
在过去十年中，已经鉴定出一个完整的膜蛋白家族——水通道蛋白，它们作为跨膜水通道发挥作用；在植物、动物和细菌界都有它们的身影。几个家族成员允许甘油和尿素通透。大多数水通道蛋白会被汞抑制。组成型表达的水通道蛋白1是近端小管、髓袢降支细段的主要通透通道，在直小血管中也有发现。水通道蛋白2在集合管主细胞中表达，在抗利尿激素的作用下，它在细胞内囊泡和顶膜之间穿梭。水通道蛋白2突变会导致肾性尿崩症；水通道蛋白2活性增加与心力衰竭、肝硬化和肾病综合征的病理生理有关。水通道蛋白3和4在集合管中提供基底外侧膜水通道。这4种通道以及其他6种通道在全身其他部位也有发现。其中几种通道的生理重要性尚不清楚。水通道蛋白1抑制剂可能会诱导有效的利尿作用，但缺乏水通道蛋白1的人没有明显的临床疾病。抗利尿激素受体拮抗剂对水通道蛋白2活性的抑制在心力衰竭、肝硬化、肾病综合征和抗利尿激素不适当分泌综合征中可能有用。
