Obestatin Downregulating Aquaporin 2 Plasma Membrane Distribution Through a Short-Term Regulatory Effect

Background

Previous studies have found that obestatin significantly inhibited water drinking and reduced the arginine vasopressin levels in the brain to decrease renal water reabsorption. However, obestatin is unable to cross the blood-brain barrier. Its effect on the body's kidney water metabolism in peripheral remains unknown.

Materials and Methods

Expression and subcellular distribution of aquaporin 2 (AQP2) were detected by immunoblotting and immunofluorescence in mouse inner medullary collecting duct-3 (mIMCD-3) cells and congestive heart failure model rats. Moreover, expression of phosphorylated AQP2 (P-AQP2; Ser256) in mIMCD-3 cells was evaluated by immunoblotting.

Results

After a 30-minute treatment with obestatin in mIMCD-3 cells and congestive heart failure model rats, the AQP2 plasma membrane distribution decreased, while AQP2 protein level, P-AQP2 (Ser256) protein level and phosphorylation ratio of AQP2 showed no significant change.

Conclusions

These findings suggest that obestatin has a short-term regulatory effect on the AQP2 plasma membrane distribution. In addition, obestatin decreases the APQ2 plasma membrane distribution probably by promoting the endocytosis of AQP2.