The mechanisms of aquaporin control in the renal collecting duct

The antidiuretic hormone arginine-vasopressin (AVP) regulates water reabsor ption in renal collecting duct principal cells. Central to its antidiuretic action in mammals is the exocytotic insertion of the water channel aquapor in-2 (AQP2) from intracellular vesicles into the apical membrane of princip al cells, an event initiated by an increase in cAMP and activation of prote in kinase A. Water is then reabsorbed from the hypotonic urine of the colle cting duct. The water channels aquaporin-3 (AQP3) and aquaporin-4 (AQP4), w hich are constitutively present in the basolateral membrane, allow the exit of water from the cell into the hypertonic interstitium. Withdrawal of the hormone leads to endocytotic retrieval of AQP2 from the cell membrane. The hormone-induced rapid redistribution between the interior of the cell and the cell membrane establishes the basis for the short term regulation of wa ter permeability. In addition water channels (AQP2 and 3) of principal cell s are regulated at the level of expression (long term regulation). This review summarizes the current knowledge on the molecular mechanisms un derlying the short and long term regulation of water channels in principal cells. In the first part special emphasis is placed on the proteins involve d in short term regulation of AQP2 (SNARE proteins, Rab proteins, cytoskele tal proteins, G proteins, protein kinase A anchoring proteins and endocytot ic proteins). In the second part, physiological and pathophysiological stim uli determining the long term regulation are discussed.