Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells.
Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells.
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甲状旁腺激素可抑制成骨细胞样细胞中的细胞质 pH 值和 DNA 合成。
DOI：
10.1152/ajpendo.1988.255.1.e9
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Hruska,KA
中科院分区：
文献类型：
--
作者：
Reid,IR;Civitelli,R;Avioli,LV;Hruska,KA
最近发现，许多激素和生长因子调节胞浆pH(Phi)，有证据表明这反过来可能影响细胞生长。我们在成骨细胞样细胞系UMR 106中检测了甲状旁腺激素(PTH)对这两个参数的影响。使用对pH敏感的荧光探针2‘，7’-bis(2-carboxyethyl)-5(6)-carboxyfluorescein的初步研究表明，这些细胞通过阿米洛利可抑制的Na+-H+交换来调节PHI。大鼠甲状旁腺素-(1-34)(RPTH)在10(-11)M时呈剂量依赖性下降，1h时最大降幅为0.1+/-0.01U。这种作用可被Forsklin复制，但在阿米洛利存在下，两种药物均不影响pHi。RPTH(半最大剂量约10(-11)M)、Forsklin和N6，2‘-O-二丁基腺苷3’，5‘-环单磷酸可减少[~3H]胸腺嘧啶核苷的掺入。二酰甘油类似物佛波酯12-肉豆蔻酸酯13-乙酸酯可增加phi和[~3H]胸腺嘧啶核苷的掺入，而阿米洛利则降低这两个指标。然而，在阿米洛利存在的情况下，rPTH仍然是[~3H]胸腺嘧啶核苷掺入的有效抑制物，即使在这种情况下它不影响Phi。结论：甲状旁腺素降低了UMR 106细胞的PHI和生长，但这些变化是可以分离的。Phi的降低可能对骨代谢有其他重要的影响，如减少细胞间的通讯，并可能与骨液室的碱化有关。
It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pHi), and there is some evidence that this in turn may influence cell growth. We have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein indicated that these cells regulate pHi by means of an amiloride-inhibitable Na+-H+ exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pHi with a half-maximal effect at 10(-11) M. At 1 h, the maximal depression of pHi was 0.1 +/- 0.01 U. This effect was reproduced by forskolin, but neither agent influenced pHi in the presence of amiloride. Incorporation of [3H]thymidine was reduced by rPTH (half-maximal dose approximately 10(-11) M), forskolin, and N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pHi and [3H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [3H]thymidine incorporation in the presence of amiloride, even though it did not affect pHi in these circumstances. It is concluded that PTH decreases pHi and growth in UMR 106 cells but that these changes can be dissociated. Depression of pHi may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment.
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