Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes

Aquaporin 4 (AQP4) is abundantly expressed in the perivascular glial endfeet in the central nervous system (CNS), where it is involved in the exchange of fluids between blood and brain. At this location, AQP4 contributes to the formation and/or the absorption of the brain edema that may arise following pathologies such as brain injuries, brain tumours, and cerebral ischemia. As vasopressin and its G-protein-coupled receptor (V1aR) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1aR by heterologous expression in Xenopus laevis oocytes. The water permeability of AQP4/V1aR-expressing oocytes was reduced in a vasopressin-dependent manner, as a result of V1aR-dependent internalization of AQP4. Vasopressin-dependent internalization was not observed in AQP9/V1aR-expressing oocytes. The regulatory interaction between AQP4 and V1aR involves protein kinase C (PKC) activation and is reduced upon mutation of Ser180 on AQP4 to an alanine. Thus, the present study demonstrates at the molecular level a functional link between the vasopressin receptor V1aR and AQP4. This functional interaction between AQP4 and V1aR may prove to be a potential therapeutic target in the prevention and treatment of brain edema.