Fig. 1.

Vasopressin (AVP, red square) binds to the type 2 vasopressin receptor (V₂R) receptor on the basolateral membrane, resulting in increased cellular cAMP via adenylyl cyclase (AC) activation. Increased cAMP activates PKA, which in turn, phosphorylates aquaporin 2 (AQP2), increases its apical membrane expression, and increases water reabsorption. Nephrogenic diabetes insipidus (NDI), either congenital (V₂R defect) or acquired (lithium), results in lowered cellular cAMP levels and lack of PKA activation and decreases AQP2 in the membrane. AG-490 increases the membrane expression of AQP2.