NDT Advance Access originally published online on January 18, 2007
Nephrology Dialysis Transplantation 2007 22(4):1078-1086; doi:10.1093/ndt/gfl713
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells*
1Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, 2Product Research Department, Chugai Pharmaceutical Co. Ltd, Shizuoka, 3The First Department of Pathology, Wakayama Medical University, Wakayama and 4Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
Correspondence and offprint requests to: Kazuhiro Shiizaki, MD PhD, Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama 641-0012, Japan. Email: shiizaki{at}wakayama-med.ac.jp
 |
Abstract |
|---|
Background. Injection of maxacalcitol (OCT) directly into the parathyroid gland (PTG) is a clinically safe and effective treatment for advanced secondary hyperparathyroidism (A-SHPT) resistant to conventional medical treatment. In the present study, the degree of nuclear localization of directly injected OCT in parathyroid cells (PTC) was investigated by microautoradiography (mARG) in a model of A-SHPT.
Methods. The 5/6 nephrectomized Sprague–Dawley rats were fed a high-phosphate and low-calcium diet for 8 weeks and consequently the level of vitamin D receptor (VDR) in their PTC severely decreased. The bilateral PTG were surgically exposed and only the left gland were directly injected with 3H-OCT (DI-3H-OCT). The time course of the changes in both radioactivity and localization of 3H-OCT in the bilateral glands was analysed using a bioimaging analyser system and mARG, respectively. A very high dose of unlabelled calcitriol was administered intravenously (IV-1,25D3) prior to DI-3H-OCT, as a competitive study.
Results. Peak radioactivity levels in the directly injected and intact PTG occured immediately and 1 h, respectively, after DI-3H-OCT, and the difference was about 50-fold higher in the treated gland. The of mARG showed a marked concentration of silver grains in the nuclei of PTC in the gland treated with DI-3H-OCT and that concentration was significantly suppressed by IV-1,25D3.
Conclusions. Direct injection of OCT into the PTG enables the administration of the highly concentrated drug for specific binding to nuclear vitamin D binding sites, including VDR of PTC, which markedly suppresses the parathyroid hormone, improves the response to calcium and vitamin D and induces apoptosis in PTC.
Keywords: 22-oxacalcitriol; 5/6 nephrectomy; parathyroid gland; renal osteodistrophy; secondary hyperparathyroidism; vitamin D receptor
Received for publication: 29. 8.06
Accepted in revised form: 2.11.06
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Shiizaki, I. Hatamura, S. Negi, E. Nakazawa, R. Tozawa, S. Izawa, T. Akizawa, and E. Kusano Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland NDT Plus, August 1, 2008; 1(suppl_3): iii42 - iii48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shiizaki, I. Hatamura, S. Negi, T. Sakaguchi, F. Saji, I. Imazeki, E. Kusano, T. Shigematsu, and T. Akizawa Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland--study in rats Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1529 - 1536. [Abstract] [Full Text] [PDF]
|
|