Requirement of Human Renal Water Channel Aquaporin-2 for Vasopressin-dependent Concentration of Urine

TLDR

Urine concentration in mammals is regulated by vasopressin, which binds V2 receptors to insert water channels in collecting duct principal cells, and failure to concentrate urine in nephrogenic diabetes insipidus indicates a defect in this pathway. The study identified a male patient with autosomal recessive nephrogenic diabetes insipidus who was a compound heterozygote for two mutations in the aquaporin‑2 gene, the kidney water channel. Functional expression in Xenopus oocytes showed both mutations produced nonfunctional aquaporin‑2 channels, confirming that aquaporin‑2 is essential for vasopressin‑dependent urine concentration.

Abstract

Concentration of urine in mammals is regulated by the antidiuretic hormone vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of water channels in apical membranes of principal cells in collecting ducts. In nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to vasopressin. A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine.