Nephrogenic Diabetes Insipidus

Abstract

The neurohypophyseal antidiuretic hormone, arginine vasopressin (AVP), stimulates urinary concentration in mammals by increasing the water permeability of renal collecting ducts and by stimulating NaCl reabsorption by thick ascending limbs of Henle into the medullary interstitium. In the collecting duct, AVP binds to specific V2 receptors (V2R) on the basolateral plasma membrane of principal cells and stimulates adenylyl cyclase, which increases cytosolic cAMP levels. The increase in cAMP activates protein kinase A (PKA) and protein phosphorylation ensues. While the nature and role of the PKA substrates remains generally obscure, one phosphorylated protein is the vasopressin-sensitive water channel, aquaporin 2 (AQP2), which relocates from a pool of intracellular vesicles to the apical plasma membrane of principal cells upon vasopressin stimulation. This exocytotic insertion of water channels, illustrated in Fig. 69-1, greatly increases the water permeability of the principal cell apical membrane. Because the basolateral membrane of principal cells has a constitutively high water permeability because of the presence of two other water channels, AQP3 and AQP4, this vasopressin-induced apical exocytotic process is the rate-limiting step for increasing collecting duct epithelial cell water permeability. The urine in the tubule lumen equilibrates osmotically with the hypertonic interstitium by the bulk flow of water across the collecting duct principal cells, and the urine is concentrated.KeywordsWater ChannelPrincipal CellNephrogenic Diabetes InsipidusVasopressin ReceptorAQP2 GeneThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.