| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Unidad de Investigacion, Servicio de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Avda Menendez Pidal s/n, Spain
2 Dept. Biologia Ambiental y Salud Publica, Universidad de Huelva, Huelva, Avda. Fuerzas Armadas s/n, Spain
3 Dept. Medicina y Cirugia Animal, Universidad de Cordoba, Cordoba, Ctra. Madrid-Cadiz, Spain
4 Dept. Medicina y Cirugia Animal, Universidad de Huelva, Cordoba, Ctra. Madrid-Cadiz, Spain
5 Department of Metabolic Disorders, Amgen Inc, Thousand Oaks, California, United States
6 Unidad de Investigación, Servicio de Nefrologia, Hospital Universitario Reina Sofía, Cordoba, Spain
* To whom correspondence should be addressed. E-mail: pv1agtee{at}uco.es.
We have 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 to 1 µM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in mean ± SE VDR expression. Incubation in 1 mM calcium + 0.001 µM R-568 elicited an increase in VDR mRNA (306% ± 46%) similar to the maximum increase detected (1.5 mM calcium) (330% ± 42%). In vivo, VDR mRNA was increased after administration of either R-568 (168% ± 9%, P < 0.001 versus control) or calcitriol (198% ± 16%, P < 0.001 versus 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.
This article has been cited by other articles:
|
|
 |
|
  L. Kantham, S. J. Quinn, O. I. Egbuna, K. Baxi, R. Butters, J. L. Pang, M. R. Pollak, D. Goltzman, and E. M. Brown The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E915 - E923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yokoyama Cinacalcet Hydrochloride in Chronic Kidney Disease-Mineral Bone Disorder Clin. J. Am. Soc. Nephrol., September 1, 2009; 4(9): 1405 - 1408. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nechama, I. Z. Ben-Dov, J. Silver, and T. Naveh-Many Regulation of PTH mRNA stability by the calcimimetic R568 and the phosphorus binder lanthanum carbonate in CKD Am J Physiol Renal Physiol, April 1, 2009; 296(4): F795 - F800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Komaba and M. Fukagawa Regression of parathyroid hyperplasia by calcimimetics--fact or illusion? Nephrol. Dial. Transplant., March 1, 2009; 24(3): 707 - 709. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Mendoza, I. Lopez, R. Canalejo, Y. Almaden, D. Martin, E. Aguilera-Tejero, and M. Rodriguez Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats Am J Physiol Renal Physiol, March 1, 2009; 296(3): F605 - F613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Komaba, M. Tanaka, and M. Fukagawa Reply Nephrol. Dial. Transplant., February 1, 2009; 24(2): 691 - 692. [Full Text] [PDF]
|
|
|
|
|
|
T. B. Drueke and E. Ritz Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives Clin. J. Am. Soc. Nephrol., January 1, 2009; 4(1): 234 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Carrillo-Lopez, D. Alvarez-Hernandez, I. Gonzalez-Suarez, P. Roman-Garcia, J. M. Valdivielso, J. L. Fernandez-Martin, and J. B. Cannata-Andia Simultaneous changes in the calcium-sensing receptor and the vitamin D receptor under the influence of calcium and calcitriol Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3479 - 3484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Maiti, N. C. Hait, and M. J. Beckman Extracellular Calcium-sensing Receptor Activation Induces Vitamin D Receptor Levels in Proximal Kidney HK-2G Cells by a Mechanism That Requires Phosphorylation of p38{alpha} MAPK J. Biol. Chem., January 4, 2008; 283(1): 175 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Drueke, D. Martin, and M. Rodriguez Reply Nephrol. Dial. Transplant., January 1, 2008; 23(1): 408 - 409. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Frazao and M. Rodriguez Secondary Hyperparathyroidism Disease Stabilization Following Calcimimetic Therapy NDT Plus, January 1, 2008; 1(suppl_1): i12 - i17. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
