Molecular Physiology of Renal Aquaporins and Sodium Transporters: Exciting Approaches to Understand Regulation of Renal Water Handling

摘要

The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water crosses biologic membranes specifically, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. The importance of this achievement is underscored by awarding Peter Agre the Nobel Prize in chemistry in 2003. Of the known twelve aquaporin isoforms, at least eight are known to be present in the kidney at distinct sites along the nephron and collecting duct. AQP1 is extremely abundant in the proximal tubule and descending thin limb where it appears to be the main site for proximal nephron water reabsorption. AQP1 is also present in the descending vasa recta. AQP2 is abundant in the collecting duct principal cells and is the chief target for the regulation of collecting duct water reabsorption by vasopressin. Acute regulation involves vasopressin-induced trafficking of AQP2 between an intracellular reservoir in vesicles and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational control of body water balance, which is achieved through regulation of AQP2 expression. Importantly, multiple studies have now underscored a critical role of AQP2 in several inherited and acquired water balance disorders. This includes inherited forms of nephrogenic diabetes insipidus, acquired states of nephrogenic diabetes insipidus, and other diseases associated with urinary concentrating defects where AQP2 expression and targeting is affected as recently reviewed (1).