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 (V1(a)R) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1(a)R by heterologous expression in Xenopus laevis oocytes. The water permeability of AQP4/V1(a)R-expressing oocytes was reduced in a vasopressin-dependent manner, as a result of V1(a)R-dependent internalization of AQP4. Vasopressin-dependent internalization was not observed in AQP9/V1(a)R-expressing oocytes. The regulatory interaction between AQP4 and V1(a)R involves protein kinase C (PKC) activation and is reduced upon mutation of Ser(180) on AQP4 to an alanine. Thus, the present study demonstrates at the molecular level a functional link between the vasopressin receptor V1(a)R and AQP4. This functional interaction between AQP4 and V1(a)R may prove to be a potential therapeutic target in the prevention and treatment of brain edema.
Department of Anatomy, Nordic Center of Excellence for Water Imbalance Related Disorders, The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark.
H B
HB
Moeller
R A
RA
Fenton
T
T
Zeuthen
N
N
Macaulay
D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009865:Oocytes / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010539:Permeability; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000096:biosynthesis / Q000235:genetics; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014667:Vasopressins / Q000502:physiology*; D014867:Water / Q000378:metabolism; D014982:Xenopus laevis
D051401:Aquaporin 4; D017483:Receptors, Vasopressin; D014867:Water; D014667:Vasopressins; D012694:Serine; D011493:Protein Kinase C