Aquaporin-2 (AQP2), the
vasopressin-regulated
water channel of the renal collecting duct, is dysregulated in numerous disorders of water balance in people and animals, including those associated with
polyuria (urinary tract obstruction,
hypokalemia,
inflammation, and
lithium toxicity) and with dilutional
hyponatremia (syndrome of inappropriate antidiuresis,
congestive heart failure,
cirrhosis). Normal regulation of AQP2 by
vasopressin involves 2 independent regulatory mechanisms: (1) short-term regulation of AQP2 trafficking to and from the apical plasma membrane, and (2) long-term regulation of the total abundance of the
AQP2 protein in the cells. Most disorders of water balance are the result of dysregulation of processes that regulate the total abundance of AQP2 in collecting duct cells. In general, the level of AQP2 in a collecting duct cell is determined by a balance between production via translation of AQP2
mRNA and removal via degradation or secretion into the urine in exosomes. AQP2 abundance increases in response to
vasopressin chiefly due to increased translation subsequent to increases in AQP2
mRNA.
Vasopressin-mediated regulation of AQP2 gene transcription is poorly understood, although several
transcription factor-binding elements in the 5' flanking region of the AQP2 gene have been identified, and candidate
transcription factors corresponding to these elements have been discovered in proteomics studies. Here, we review progress in this area and discuss elements of
vasopressin signaling in the collecting duct that may impinge on regulation of AQP2 in health and in the context of examples of polyuric diseases.