| Abstract | 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. |
| Authors | M E Rodriguez, Y Almaden, S Cañadillas, A Canalejo, E Siendones, I Lopez, E Aguilera-Tejero, D Martin, M Rodriguez
(Affiliation: Unidad de Investigacion, Servicio de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Spain.)
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| Journal | American journal of physiology. Renal physiology
(Am J Physiol Renal Physiol)
Vol. 292
Issue 5
Pg. F1390-5
(May 2007)
ISSN: 0363-6127 United States |
| PMID | 17200160
(Publication Type: In Vitro, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Aniline Compounds
- Drug Combinations
- N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
- Parathyroid Hormone
- RNA, Messenger
- Receptors, Calcitriol
- Calcitriol
- Calcium
|
| Topics |
- Aniline Compounds
(administration & dosage, pharmacology)
- Animals
- Calcitriol
(pharmacology)
- Calcium
(agonists, pharmacology)
- Dose-Response Relationship, Drug
- Drug Combinations
- Humans
- Hyperparathyroidism
(metabolism, pathology)
- Hyperplasia
- Male
- Parathyroid Glands
(drug effects, metabolism, pathology)
- Parathyroid Hormone
(antagonists & inhibitors, secretion)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Receptors, Calcitriol
(genetics, metabolism)
|
