The calcium-sensing receptor regulates calcium absorption in MDCK cells byinhibition of PMCA

Calcium transport across a monolayer of Madin-Darby canine kidney (MDCK) ce lls was measured in response to stimulation of the basal surface with calci um-sensing receptor (CaR) agonists. Stimulation of the CaR resulted in a ti me- and concentration-dependent inhibition of calcium transport but did not change transepithelial voltage or resistance. Inhibition of transport was not altered by pretreatment of cells with pertussis toxin but was blocked b y the phospholipase C (PLC) inhibitor U-73122. To determine a potential mec hanism by which the CaR could inhibit calcium transport, we measured activi ty of the plasma membrane calcium ATPase (PMCA). Stimulation of the CaR on the basal surface resulted in an inhibition of the PMCA in a concentration- and PLC-dependent manner. Thus stimulation of the CaR inhibits both calcium transport and PMCA activity through a PLC-dependent pathway. These studies provide the first direct evidence that calcium can inhibit its own transce llular absorption in a model of the distal tubule. In addition, they provid e a potential mechanism for the CaR to inhibit calcium transport, inhibitio n of PMCA.