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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1390    most recent 00262.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Rodriguez, M. E. Articles by Rodriguez, M. Search for Related Content PubMed PubMed Citation Articles by Rodriguez, M. E. Articles by Rodriguez, M.

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands

¹Unidad de Investigacion, Servicio de Nefrologia, Hospital Universitario Reina Sofia, ²Department of Medicina y Cirugia Animal, Universidad de Cordoba, Cordoba, ³Department of Biología Ambiental y Salud Pública, Universidad de Huelva, Huelva, Spain; and ⁴Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, California

Submitted 11 July 2006 ; accepted in final form 11 December 2006

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001–1 µM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean ± SE). Incubation in 1 mM calcium + 0.001 µM R-568 elicited an increase in VDR mRNA (306 ± 46%) similar to the maximum increase detected with 1.5 mM calcium (330 ± 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 ± 9%, P < 0.001 vs. control) or calcitriol (198 ± 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

calcium; parathyroid hormone

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