Sun F, Ritchie C K, Hassager C, Maercklein P, Fitzpatrick L A
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905.
J Clin Invest. 1993 Feb;91(2):595-601. doi: 10.1172/JCI116239.
Classical stimulus-secretion theory suggests that each individual cell responds to a given stimulus. We tested this theory by determining the response of single bovine parathyroid cells to calcium with the reverse hemolytic plaque assay (RHPA), an assay that measures hormone release from individual cells. As calcium concentrations decreased, the amount of parathyroid hormone (PTH) released per cell increased, and cells were recruited to release PTH. To confirm that adequate stores of PTH were present, immunocytochemistry and in situ hybridization were performed. To test if cells that did not release PTH were capable of secretion, we performed a sequential RHPA; 47.8% of cells did not release PTH after the first stimulus. After the second exposure to low concentrations of calcium, 26.5% of these "nonsecretory" cells were able to release PTH. We conclude that parathyroid cells are homogeneous for PTH content and synthetic capability. Parathyroid cells respond to changes in extracellular calcium heterogeneously in that more PTH per cell is released, and individual parathyroid cells are "recruited" to release PTH at low calcium concentrations. In addition, parathyroid cells can be induced to secrete suggesting that cells are viable but in a depressed secretory state. Parathyroid cells may exist in an "on" or "off" secretory state.
经典的刺激-分泌理论认为，每个细胞都会对特定的刺激做出反应。我们通过使用反向溶血空斑试验（RHPA）来测定单个牛甲状旁腺细胞对钙的反应，从而验证了这一理论。RHPA是一种用于测量单个细胞激素释放量的试验。随着钙浓度的降低，每个细胞释放的甲状旁腺激素（PTH）量增加，并且有更多细胞开始释放PTH。为了确认细胞中存在足够的PTH储备，我们进行了免疫细胞化学和原位杂交实验。为了测试未释放PTH的细胞是否具有分泌能力，我们进行了连续RHPA实验；在第一次刺激后，47.8%的细胞未释放PTH。在第二次暴露于低钙浓度后，这些“非分泌性”细胞中有26.5%能够释放PTH。我们得出结论，甲状旁腺细胞在PTH含量和合成能力方面是同质的。甲状旁腺细胞对细胞外钙变化的反应具有异质性，即每个细胞释放的PTH更多，并且在低钙浓度下，单个甲状旁腺细胞会被“动员”来释放PTH。此外，甲状旁腺细胞可以被诱导分泌，这表明细胞是有活力的，但处于分泌受抑制的状态。甲状旁腺细胞可能处于“开启”或“关闭”的分泌状态。
