Calcium sensing receptor exerts a negative regulatory action toward vasopressin-induced aquaporin-2 expression and trafficking in renal collecting duct.

Abstract

Vasopressin (AVP) plays a major role in the regulation of water homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. An increase in plasma sodium concentration stimulates AVP release, which in turn promotes water reabsorption. Upon binding to the V2 receptors in the renal collecting duct, AVP induces the expression and apical membrane insertion of the aquaporin-2 (AQP2) water channels and subsequent water reabsorption. AVP regulates two independent mechanisms: the short-term regulation of AQP2 trafficking and long-term regulation of the total abundance of the AQP2 protein in the cells. On the other hand, several hormones, acting through specific receptors, have been reported to antagonize AVP-mediated water transport in kidney. In this respect, we previously described that high luminal Ca2+ in the renal collecting duct attenuates short-term AVP-induced AQP2 trafficking through activation of the Ca2+-sensing receptor (CaSR). This effect is due to reduction of AVP-dependent cAMP generation and possibly hydrolysis. Moreover, CaSR signaling reduces AQP2 abundance both via AQP2-targeting miRNA-137 and the proteasomal degradation pathway. This chapter summarizes recent data elucidating the molecular mechanisms underlying the physiological role of the CaSR-dependent regulation of AQP2 expression and trafficking.