Calcitonin-stimulated renal Ca2+ reabsorption occurs independently of TRPV5.

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CT augments the renal reabsorptive capacity for Ca(2+). This increase is likely to occur independently of TRPV5.