PTH Modulation of NCC Activity Regulates TRPV5 Calcium Reabsorption.

PTH Modulation of NCC Activity Regulates TRPV5 Calcium Reabsorption. Am J Physiol Renal Physiol. 2015 Nov 25;:ajprenal.00323.2015 Authors: Hoover RS, Tomilin V, Hanson LN, Pochynyuk O, Ko B Abstract Since parathyroid hormone (PTH) is known to increase TRPV5 activity and decrease NCC activity, we hypothesized that decreased NCC-mediated sodium reabsorption contributes to the enhanced TRPV5 calcium reabsorption seen with PTH. To test this, we implemented mDCT15 cells expressing functional TRPV5 and ruthenium red sensitive 45Ca2+ uptake. PTH increased 45Ca2+ uptake to 8.8±0.7 nmol/mg/min (n=4, p<0.01) and decreased NCC activity from 75.4±2.7 to 20.3±1.3 nmol/mg/min (n=4, p<0.01). Knockdown of RasGRP1 had no baseline effect on 45Ca2+ uptake but significantly attenuated the response to PTH from a 45% increase (6.0±0.2 to 8.7±0.4 nmol/mg/min) in controls to only 20% in knockdown cells (6.1±0.1 to 7.3±0.2 nmol/mg/min (n=4, p<0.01)). Inhibition of PKC and PKA resulted in further attenuation of the PTH effect. RasGRP1 knockdown decreased the magnitude of the TRPV5 response to PTH (7.9±0.1 nmol/mg/min for knockdown compared to 9.1±0.1 nmol/mg/min in control), and the addition of thiazide eliminates this effect (a nearly identical 9.0±0.1 nmol/mg/min). This indicates that functionally active NCC is required for RasGRP1 knockdown to impact the PTH effect on TRPV5 activity. Knockdown of WNK4 resulted in an attenuation of the in...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research