Description
Aquaporin 2 also called Aquaporin-CD, is found in the apical cell membranes of the kidneys collecting duct principal cells and in intracellular vesicles located throughout the cell. The AQP2 gene is mapped to chromosome 12q13, very close to the site of major intrinsic protein by situ hybridization. Investigators suggest that a defect in the gene is the basis of the autosomal form of nephrogenic diabetes insipidus. The functional expression and the limited localization suggested that AQP2 is the vasopressin-regulated water channel. Using rat kidney slices and porcine kidney cells stably expressing rat Aquaporin 2, trafficking can be stimulated by cAMP-independent pathways that utilize nitric oxide(NO). The NO donors sodium nitroprusside(SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of vasopressin(VP), stimulating relocation of Aquaporin 2 from cytoplasmic vesicles to the apical plasma membrane. SNP increased intracellular cGMP rather than cAMP, and exogenous cGMP stimulated AQP2 membrane insertion. Atrial natriuretic factor, which signals via cGMP, also stimulated AQP2 translocation. Expression in kidney connecting tubules is sufficient for survival and that expression in collecting ducts is required to regulate body water balance. The S256L substitution in the cytoplasmic tail of the protein prevented phosphorylation at S256 and the subsequent accumulation of Aquaporin 2 on the apical membrane of the collecting duct principal cells