Effect of 1,25-dihydroxyvitamin D3 on cyclic AMP responses to hormones in clonal osteogenic sarcoma cells.
Effect of 1,25-dihydroxyvitamin D3 on cyclic AMP responses to hormones in clonal osteogenic sarcoma cells.
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1,25-二羟基维生素 D3 对克隆成骨肉瘤细胞中环 AMP 对激素反应的影响。
DOI：
10.1042/bj2310011
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发表时间：
1985
影响因子：
4.1
通讯作者：
T. Martin
中科院分区：
文献类型：
--
作者：
M. Kubota;K. Ng;T. Martin
在克隆成骨肉瘤细胞系UMR 106-06中研究了1，25-二羟维生素D3对腺苷酸环化酶反应性的影响，该细胞系对几种骨活性激素有反应。1，25-二羟维生素D3治疗对完整细胞中环AMP的基础形成没有一致的影响，但对甲状旁腺激素、异丙肾上腺素、前列腺素E2、鲑鱼降钙素和植物二萜类、毛喉素的反应均减弱，最高达90%。1，25-二羟维生素D3的作用是剂量依赖性的，在0.1 nM时具有半数最大有效性，并且需要48小时的细胞处理才变得明显。其他维生素D3化合物的相对效力与它们对1，25-二羟基维生素D3受体的相对亲和力及其在其他系统中的生物活性密切相关。1，25-二羟维生素D3处理对标记降钙素与UMR 106-06细胞结合的动力学没有影响。此外，这样一系列激素受到影响的事实使得受体介导的机制不太可能。核苷酸刺激（Ns）单位活性测定后，1，25-二羟维生素D3治疗，发现是不变的。胰岛活化蛋白，核苷酸抑制单位（Ni）活性的抑制剂，未能修改1，25-二羟维生素D3的效果。因此，1，25-二羟维生素D3的作用似乎超出了激素受体和腺苷酸环化酶复合物的核苷酸调节组分。它的结论是，1，25-二羟维生素D3衰减腺苷酸环化酶的催化组分上的直接或间接的作用激素的腺苷酸环化酶的反应。
The effect of 1,25-dihydroxyvitamin D3 on adenylate cyclase responsiveness was studied in the clonal osteogenic sarcoma cell line, UMR 106-06, which responds to several bone active hormones. 1,25-dihydroxyvitamin D3 treatment had no consistent effect on basal formation of cyclic AMP in intact cells, but the responses to parathyroid hormone, isoproterenol, prostaglandin E2, salmon calcitonin and the plant diterpene, forskolin, were all attenuated, by up to 90%. The effect of 1,25-dihydroxyvitamin D3 was dose-dependent, with half-maximal effectiveness at 0.1 nM, and required 48 h treatment of cells before it became apparent. The relative potencies of other vitamin D3 compounds correlated closely with their relative affinities for the 1,25-dihydroxyvitamin D3 receptor and their biological activities in other systems. 1,25-dihydroxyvitamin D3 treatment had no effect on the kinetics of labelled calcitonin binding to UMR 106-06 cells. Furthermore, the fact that such a range of hormones was affected made a receptor mediated mechanism unlikely. Nucleotide stimulatory (Ns) unit activity was assayed after 1,25-dihydroxyvitamin D3 treatment and found to be unchanged. Islet activating protein, an inhibitor of nucleotide inhibitory unit (Ni) activity, failed to modify the 1,25-dihydroxyvitamin D3 effect. Thus the effect of 1,25-dihydroxyvitamin D3 appeared to be exerted beyond hormone receptor and nucleotide regulatory components of the adenylate cyclase complex. It is concluded that 1,25-dihydroxyvitamin D3 attenuates adenylate cyclase response to hormones by a direct or indirect action on the catalytic component of adenylate cyclase.