Nephrogenic diabetes insipidus (NDI) is characterized by insensitivity
of the distal renal nephron to the antidiuretic effect of the neurohy
pophyseal hormone arginine vasopressin. In the last 2 years, two diffe
rent genetic defects causing the NDI phenotype have been identified. T
he genes involved encode proteins that reside at both ends of the cell
ular vasopressin signaling cascade, namely the vasopressin V-2 recepto
r and the aquaporin-2 water channel. Analysis of naturally occurring m
utations in the V-2 receptor and the aquaporin-2 water channel will fa
cilitate the study of structure-function correlates of both proteins,
which will lead to substantial progress in elucidating the cellular me
chanisms involved in the antidiuretic effect of vasopressin.