Calcitonin-stimulated renal Ca2+ reabsorption occurs independently of TRPV5

Abstract

Calcitonin (CT) is known to affect renal Ca(2+) handling. However, it remains unclear how CT affects Ca(2+) transport in the distal convolutions. The aim of this study was to investigate the contribution of the renal epithelial Ca(2+) channel, transient receptor potential vanilloid 5 (TRPV5), to renal Ca(2+) handling in response to CT. C57BL/6 mice received a single overnight (16 hr) injection of CT. In addition, TRPV5 knockout (TRPV5(-/-)) mice and their wild type (TRPV5(+/+)) controls, received three bolus injections of CT over a 40 hr study period. All experimental groups were placed in metabolic cages. C57BL/6 mice received a single bolus injection of CT, which significantly reduced the urinary Ca(2+) excretion. In addition, urinary Na(+) and K(+) excretion also decreased after CT administration. No apparent changes in renal expression of TRPV5, calbindin-D(28K) (CaBP28K) or TRPV6 could be detected between CT- and vehicle-treated mice. To evaluate whether TRPV5 activity is needed for the CT-induced increase in Ca(2+) reabsorption, mice with genetic ablation of TRPV5 (TRPV5(-/-)) were employed. TRPV5(-/-) mice as well as their wild-type (TRPV5(+/+)) controls received three bolus injections of CT over a 40-hr study period. Overnight (16 hrs) as well as the subsequent 24-hr urine was collected. Overnight urinary Ca(2+) excretion was reduced in both TRPV5(-/-) and TRPV5(+/+) mice after a bolus injection of CT. The subsequent 24-hr urinary excretion of Ca(2+) which was collected after the third bolus injection showed no effect of CT on renal Ca(2+) handling in either mice group. Accordingly, CT did not alter the intrarenal protein abundance of TRPV5 and CaBP28K after three bolus injections of CT. CT augments the renal reabsorptive capacity for Ca(2+). This increase is likely to occur independently of TRPV5.