NEOMYCIN MIMICS THE EFFECTS OF HIGH EXTRACELLULAR CALCIUM CONCENTRATIONS ON PARATHYROID FUNCTION IN DISPERSED BOVINE PARATHYROID CELLS
NEOMYCIN MIMICS THE EFFECTS OF HIGH EXTRACELLULAR CALCIUM CONCENTRATIONS ON PARATHYROID FUNCTION IN DISPERSED BOVINE PARATHYROID CELLS
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DOI：
10.1210/endo-128-6-3047
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发表时间：
1991-06-01
期刊：
影响因子：
4.8
通讯作者：
KIFOR, O
中科院分区：
文献类型：
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作者：
BROWN, EM;BUTTERS, R;KIFOR, O
我们研究了聚阳离子抗生素新霉素对分散的牛甲状旁腺细胞功能的影响。 新霉素引起可逆的，剂量依赖性抑制低钙（Ca++）刺激的PTH释放，在30 μ M的半最大抑制。 最大抑制（与200 μ M新霉素）是不加性的抑制作用的高（2 mM）Ca++。 在100-200 μ M时，新霉素还抑制多巴胺刺激的cAMP积累90-98%，在40-50 μ M时具有半数最大效应。 这种作用是可逆的，并通过用0.5 μ g/ml百日咳毒素预孵育细胞过夜来阻断。 除了对cAMP代谢和PTH释放的抑制作用外，新霉素还刺激了磷酸肌醇的积累，并在fura-2负载的甲状旁腺细胞中产生胞质Ca++浓度（Ca（i））的瞬时增加。 尽管细胞外Ca++被去除，但新霉素诱发的Ca（i）峰持续存在，表明其来自细胞内Ca++储存。 细胞暴露于升高的镁（Mg++）浓度引起Ca（i）的类似尖峰，但响应于随后加入新霉素而阻断Ca（i）的尖峰，反之亦然。 因此，Mg++和新霉素从相同的细胞内储存中动员Ca++。 这些结果表明，聚阳离子，新霉素，密切模仿多价阳离子对甲状旁腺功能的影响，这表明这两种药物通过类似的生化途径调节甲状旁腺功能。
We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells. Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30-mu-M. Maximal inhibition (with 200-mu-M neomycin) was not additive with the suppressive effects of high (2 mM) Ca++. Neomycin also inhibited dopamine-stimulated cAMP accumulation by 90-98% at 100-200-mu-M, with a half-maximal effect at 40-50-mu-M. This action was reversible and was blocked by preincubating the cells overnight with 0.5-mu-g/ml pertussis toxin. In addition to its suppressive effects on cAMP metabolism and PTH release, neomycin stimulated the accumulation of inositol phosphates and produced a transient increase in the cytosolic Ca++ concentration (Ca(i)) in fura-2-loaded parathyroid cells. The neomycin-evoked spike in Ca(i) persisted despite removal of extracellular Ca++, indicating that it arises from intracellular Ca++ stores. Exposure of cells to elevated magnesium (Mg++) concentrations elicited a similar spike in Ca(i) but blocked the spike in Ca(i) in response to subsequent addition of neomycin and vice versa. Thus, Mg++ and neomycin mobilize Ca++ from the same intracellular store(s). These results indicate that a polycation, neomycin, closely mimics the effects of polyvalent cations on parathyroid function, suggesting that both agents regulate parathyroid function via similar biochemical pathways.