Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.
Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.
复制标题
器官培养中的骨吸收：二价阳离子离子载体 A23187 和 X-537A 的抑制。
DOI：
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发表时间：
1976
影响因子：
15.9
通讯作者：
A. Tashjian
中科院分区：
文献类型：
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作者：
J. Ivey;D. R. Wright;A. Tashjian
以A23187和X-537A离子载体为探针，探讨骨摄取钙在甲状旁腺激素(PTH)等药物刺激小鼠颅骨骨吸收中的可能作用。单独的离子载体在1 NM到20微米的浓度范围内不能刺激骨吸收，也不能增强短时间(15-60分钟)或长时间(1-3天)的次最大浓度的甲状旁腺素刺激的骨吸收。出乎意料的是，我们发现这些离子载体以剂量依赖的方式抑制PTH和其他各种化合物(前列腺素E2、1α-羟基胆钙化醇、3-异丁基-1-甲基-黄嘌呤和佛波酯)刺激的骨吸收。这种抑制不是由于离子载体对骨骼的不可逆损害，因为即使在处理24小时后，这种抑制也是可逆的。在高钙和低钙条件下，离子载体对骨吸收均有抑制作用，说明这种抑制作用不是由于细胞外钙浓度的限制。离子载体的抑制作用在几个方面与降钙素产生的抑制作用有质的不同，降钙素是一种天然的骨吸收抑制剂。此外，1.0µg/ml的A23187对对照组、甲状旁腺素或降钙素处理的颅骨培养上清液中cAMP的积聚均无影响。我们的结论是，离子载体A23187或X537A既不刺激骨吸收，也不增强骨吸收刺激剂的作用；相反，它们是多种化合物刺激的骨吸收的抑制剂。
The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 muM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, 1alpha-hydroxycholecalciferol, 3-isobutyl-1-methyl-xanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria. We conclude that the ionophores A23187 or X537A do not stimulate bone resorption nor potentiate the effects of stimulators of bone resorption; instead they are inhibitors of bone resorption stimulated by a wide variety of compounds.