1999 European Regional Conference Proceeding
May 12 - 16, 1999
|Conference:||1999 European Regional Conference|
|Title:||Long-term regulation of aquaporin-2: a possible therapeutic approach to NDI?|
|Institution:||University of Leeds|
The kidney collecting ducts are responsible for helping control the body's water balance. They do this by allowing the kidney to reabsorb much of the body water that flows through them. The kidneys are able to reabsorb the body water flowing through the collecting ducts when a protein called aquaporin-2 (AQP2) is inserted into the apical membrane of the principal cells that line the collecting ducts. AQP2s then act as channels through which much greater amounts of body water can pass into the kidney than when AQP2s are not present in the apical membranes.
The signal that sends the AQP2s to the apical membranes occurs when the antidiuretic hormone, vasopressin (VP), binds to the vasopressin-2 receptor, located in the basolateral membrane of the collecting duct principal cells. In nephrogenic diabetes insipidus (NDI), AQP2s are unable to perform their water channeling function. Because of this, the kidneys cannot reabsorb the body water flowing through the collecting ducts and the unabsorbed water leaves the body as excessive urine.
NDI can either be inherited or acquired, and in both cases the number of AQP2s that are expressed in the collecting duct principal cells are reduced. Studies have demonstrated that the number of AQP2s that are expressed in these cells can be controlled by molecular pathways that are both dependent on and independent of VP binding with its V2 receptors. Research is now focused on acquiring a deeper understanding of the different molecular pathways involved in AQP2 expression. Marples suggests that if researchers learn how to activate molecular pathways that increase the number of AQP2s in the principal cells, they may be able to develop treatments for many of the acquired forms of NDI. These treatments might also help reduce the excessive urination associated with some hereditary forms of NDI. One possible approach might be to stimulate the production of prostaglandins, molecules often associated with inflammation, but which seem to increase production of AQP2 in the kidney.