Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells
| Autor: | Toshifumi Sakaguchi, Tadashi Okada, Shigeo Negi, Ikuo Imazeki, Naohiko Hayakawa, Tadao Akizawa, Ikuji Hatamura, Kazuhiro Shiizaki, Takashi Shigematsu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Calcitriol Parathyroid hormone Antineoplastic Agents Apoptosis Calcitriol receptor Injections Parathyroid Glands Rats Sprague-Dawley Internal medicine medicine Animals Vitamin D Uremia Transplantation Hyperparathyroidism business.industry Parathyroid chief cell medicine.disease Rats Disease Models Animal Vitamin D binding Endocrinology medicine.anatomical_structure Parathyroid Hormone Nephrology Receptors Calcitriol Calcium Hyperparathyroidism Secondary Secondary hyperparathyroidism Parathyroid gland business Protein Binding medicine.drug |
| Zdroj: | Nephrology Dialysis Transplantation. 22:1078-1086 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfl713 |
| Popis: | 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 3 H-OCT (DI- 3 H-OCT). The time course of the changes in both radioactivity and localization of 3 H-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- 3 H-OCT, as a competitive study. Results. Peak radioactivity levels in the directly injected and intact PTG occured immediately and 1 h, respectively, after DI- 3 H-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- 3 HOCT 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. |
| Databáze: | OpenAIRE |
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