V2 and V1a receptor antagonists were able to rescue mutant V2 receptors by promoting their proper folding and maturation . This resulted in the expression of functional cell surface V2 receptors.
lIn a pilot study, a nonpeptide V1a receptor antagonist was administered to five men with nephrogenic
DI (each with one of three identified mutations in the V2 gene that codes for the V2 receptor)
lThis resulted in an increase in urine osmolality from a mean of 100 to 150 mosm/kg, and reductions in urine volume from 12 to 8 L/day and in water intake from 11 to 7 L/day.
lMost aquaporin-2 mutations associated with nephrogenic DI also result in proteins being retained in the intracellular space
lResearch to find chaperone-like molecules to help direct these proteins to the cell surface is ongoing.