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- Title
Coordinated control of renal Ca<sup>2+</sup> transport proteins by parathyroid hormone.
- Authors
van Abel, Monique; Hoenderop, Joost G. J.; van der Kemp, Annemiete W. C. M.; Friedlaender, Michael M.; van Leeuwen, Johannes P. T. M.; Bindels, René J. M.
- Abstract
Background. The kidney is one of the affected organs involved in the clinical symptoms of parathyroid hormone (PTH)-related disorders, like primary hyperparathyroidism and familial hypocalciuric hypercalcemia. The molecular mechanism(s) underlying alterations in renal Ca2+ handling in these disorders is poorly understood. Methods. Parathyroidectomized and PTH-supplemented rats and mice infused with the calcimimetic compound NPS R-467 were used to study the in vivo effect of PTH on the expression of renal transcellular Ca2+ transport proteins, including the epithelial Ca2+ channel transient receptor potential, vanilloid, member 5 (TRPV5), calbindins, and the Na+/Ca2+-exchanger (NCX1). In addition, the effect of PTH on transepithelial Ca2+ transport in rabbit connecting tubule/cortical collecting duct (CNT/CCD) primary cultures was determined. Results. Decreased PTH levels in parathyroidectomized rats or NPS R-467–infused mice, resulted in reduced expression of these proteins, which is consistent with diminished Ca2+ reabsorption, causing the development of the observed hypocalcemia. PTH supplementation of parathyroidectomized rats restored the expression of the renal Ca2+ transport machinery and serum Ca2+ levels, independent of serum 1,25-dihydroxyvitamin D3 levels and renal vitamin D or Ca2+-sensing receptor mRNA abundance. Inhibition of the PTH-stimulated transepithelial Ca2+ transport by the TRPV5-specific inhibitor ruthenium red reduced the PTH-stimulated expression of calbindin-D28K and NCX1 in rabbit CNT/CCD primary cultures. Conclusion. PTH stimulates renal Ca2+ reabsorption through the coordinated expression of renal transcellular Ca2+ transport proteins. Moreover, the PTH-induced stimulation is enhanced by the magnitude of the Ca2+ influx through the gatekeeper TRPV5, which in turn facilitates the expression of the downstream Ca2+ transport proteins. Therefore, the renal transcellular Ca2+ transport proteins, including TRPV5, could contribute to the pathogenesis of PTH-related disorders.
- Publication
Kidney International, 2005, Vol 68, Issue 4, p1708
- ISSN
0085-2538
- Publication type
Academic Journal
- DOI
10.1111/j.1523-1755.2005.00587.x