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

Am J Physiol Renal Physiol. 2007 May;292(5):F1390-5. doi: 10.1152/ajprenal.00262.2006. Epub 2007 Jan 2.


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 microM) 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 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / administration & dosage
  • Aniline Compounds / pharmacology*
  • Animals
  • Calcitriol / pharmacology
  • Calcium / agonists*
  • Calcium / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Humans
  • Hyperparathyroidism / metabolism
  • Hyperparathyroidism / pathology
  • Hyperplasia
  • In Vitro Techniques
  • Male
  • Parathyroid Glands / drug effects*
  • Parathyroid Glands / metabolism*
  • Parathyroid Glands / pathology
  • Parathyroid Hormone / antagonists & inhibitors
  • Parathyroid Hormone / metabolism
  • Phenethylamines
  • Propylamines
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*


  • Aniline Compounds
  • Drug Combinations
  • N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
  • Parathyroid Hormone
  • Phenethylamines
  • Propylamines
  • RNA, Messenger
  • Receptors, Calcitriol
  • Calcitriol
  • Calcium