The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands
| Autor: | Sagrario Cañadillas, Ignacio González López, Mariano Rodriguez, Maria E. Rodriguez, Emilio Siendones, David Martin, Yolanda Almaden, Antonio Canalejo, Escolastico Aguilera-Tejero |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Physiology Calcimimetic Parathyroid hormone chemistry.chemical_element In Vitro Techniques Calcium Calcitriol receptor Parathyroid Glands Calcitriol Internal medicine Phenethylamines medicine Vitamin D and neurology Animals Humans RNA Messenger Rats Wistar Receptor Calcium metabolism Aniline Compounds Hyperplasia Dose-Response Relationship Drug Propylamines Hyperparathyroidism Parathyroid chief cell Rats Drug Combinations Endocrinology chemistry Parathyroid Hormone Receptors Calcitriol |
| Zdroj: | American Journal of Physiology-Renal Physiology. 292:F1390-F1395 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00262.2006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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