REQUIREMENT OF HUMAN RENAL WATER CHANNEL AQUAPORIN-2 FOR VASOPRESSIN-DEPENDENT CONCENTRATION OF URINE

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