The kidneys are the major determinants of body water and electrolyte composition. Thus, comprehending the mechanisms of water transport is essential to understanding mammalian kidney physiology and water balance. Because of its importance to human health, water permeability has been particularly well characterized in the mammalian kidney (Knepper and Burg 1983). Approximately, 180L day(-1) of glomerular filtrate is generated in an average adult human; more than 90% of this is constitutively reabsorbed by the highly water-permeable proximal tubules and descending thin limbs of Henle' loop. The ascending thin limbs and thick limbs are relatively impermeable to water and empty into renal distal tubules and ultimately into the collecting ducts. The collecting ducts are extremely important clinically in water-balance disorders, because they are the chief site of regulated water re-absorption. Basal epithelial water permeability in collecting duct principal cells is low, but the water permeability can become exceedingly high when stimulated with arginine vasopressin (AVP, also known as antidiuretic hormone (ADH)). In this regard, the toad urinary bladder behaves like the collecting duct, and it has served as an important model of vasopressin-regulated water permeability. Stimulation of this epithelium with vasopressin produces an increase in water permeability in the apical membrane, which coincides with the redistribution of intracellular particles to the cell surface (Kachadorian et al. 1975, 1977; Wade and Kachadorian 1988). These particles were believed to contain water channels. The discovery of aquaporin-1 (AQP1) by Agre and colleagues (Preston et al. 1992; Preston and Agre 1991; Smith and Agre 1991) explained the long-standing biophysical question of how water specifically crosses biological membranes, and these studies led to the identification of a whole new family of membrane proteins, the aquaporin water channels. At present, at least eight aquaporins are expressed at distinct sites in the kidney, and four members of this family (AQP1-4) have been demonstrated to play pivotal roles in the physiology and pathophysiology for renal regulation of body water balance. In the present review, we will focus on regulation of renal aquaporins and in particular how regulation of AQP2 takes place. In addition, a number of inherited and acquired conditions characterized by urinary concentration defects as well as common diseases associated with severe water retention are discussed with relation to the role of aquaporins in regulation and dysregulation of renal water transport.

Udgivelsesdato: 2009-null