In vivo time-course of receptor binding in the parathyroid gland of the vitamin D analogue [(3)H]1,25-dihydroxy-22-oxavitamin D(3) compared with [(3)H]1,25-dihydroxyvitamin D(3), determined by micro-autoradiography.
In vivo time-course of receptor binding in the parathyroid gland of the vitamin D analogue [(3)H]1,25-dihydroxy-22-oxavitamin D(3) compared with [(3)H]1,25-dihydroxyvitamin D(3), determined by micro-autoradiography.
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维生素 D 类似物 [(3)H]1,25-二羟基-22-oxavitamin D(3) 与 [(3)H]1,25-二羟基维生素 D 相比，甲状旁腺受体结合的体内时间过程
DOI：
10.1093/ndt/17.suppl_10.53
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
W. Stumpf
中科院分区：
文献类型：
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作者：
N. Koike;N. Hayakawa;K. Tokuda;K. Nishimiya;Kimitoshi Saito;W. Stumpf
1，25-二羟基-22-草酸维生素D(3)(OCT)是1，25-二羟基维生素D(3)(1，25(OH)(2)D(3)，骨化三醇)的新合成类似物，用于治疗继发性甲状旁腺功能亢进症。本研究采用甲状旁腺受体显微放射自显影技术，测定并比较OCT和1，25(OH)(2)D(3)的受体结合时程。小鼠注射[26-(3)H]OCT或[26，27-甲基-(3)H]1，25(OH)(2)D(3)4 mg/kg，分别于5、15、30min、1、2、4、8、12、24 h处死。切除甲状腺-甲状旁腺组织，制作放射自显影。在[(3)H]OCT和[(3)H]1，25(OH)(2)D(3)剂量和调整比活度相同的条件下，[(3)H]OCT的血药浓度明显低于[(3)H]1，25(OH)(2)D(3)。甲状旁腺各时间点的主要细胞核均有不同程度的标记，结缔组织细胞未见标记。[(3)H]OCT的核受体结合量等于或高于[(3)H]1，25(OH)(2)D(3)。[(3)H]OCT的核摄取在15min达到最大，高于[(3)H]1，25(OH)(2)D(3)，在注射后1h达到最大。结果表明，OCT对甲状旁腺细胞具有较高的亲和力，提示OCT具有比1，25(OH)(2)D(3)更高的治疗潜力，特别是在临床条件下，OCT具有较低的钙化作用，可以用比1，25(OH)(2)D(3)高数倍的剂量进行治疗。
1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT), is a new synthetic analogue of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol), to be used in the treatment of secondary hyperparathyroidism. This study used receptor micro-autoradiography in the parathyroid gland to determine and compare the time-course of receptor binding between OCT and 1,25(OH)(2)D(3). Mice were injected with 4 microg/kg of [26-(3)H]OCT or [26,27-methyl-(3)H]1,25(OH)(2)D(3), and killed at 5, 15, 30 min, 1, 2, 4, 8, 12, and 24 h afterwards. Thyroid-parathyroid tissue was excised and autoradiograms were prepared. Under identical conditions of dose and adjusted specific radioactivity between [(3)H]OCT and [(3)H]1,25(OH)(2)D(3), the plasma concentration of [(3)H]OCT was much lower than that of [(3)H]1,25(OH)(2)D(3). In the parathyroid at all time points, chief cell nuclei were labelled with varying degrees while connective tissue cells remained unlabelled. Nuclear receptor binding of [(3)H]OCT appeared equal to or higher than that of [(3)H]1,25(OH)(2)D(3). Nuclear uptake of [(3)H]OCT was maximal at 15 min and higher than that of [(3)H]1,25(OH)(2)D(3), which was maximal at 1 h after injection. Low levels of nuclear retention of the two compounds were still similarly detectable at 12 h. The results indicate the high affinity of OCT to parathyroid cells, and suggest that OCT has a higher therapeutic potential than 1,25(OH)(2)D(3), especially under clinical conditions, at which OCT with its lower calcaemic effect would allow treatment with a dose several times higher than 1,25(OH)(2)D(3).
小林、园子：血。
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