Relationship of thyrotropin-releasing hormone-induced spike and plateau phases in cytosolic free Ca2+ concentrations to hormone secretion. Selective blockade using ionomycin and nifedipine.
Relationship of thyrotropin-releasing hormone-induced spike and plateau phases in cytosolic free Ca2+ concentrations to hormone secretion. Selective blockade using ionomycin and nifedipine.
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DOI：
10.1016/s0021-9258(17)42556-7
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发表时间：
1984-12
期刊：
影响因子：
--
通讯作者：
P. Albert;A. Tashjian
中科院分区：
文献类型：
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作者：
P. Albert;A. Tashjian
在克隆大鼠垂体细胞（GH细胞），促甲状腺激素释放激素（TRH）诱导的细胞内游离钙浓度的变化模式[（Ca 2+）i）由两个阶段组成：一个急性尖峰期微摩尔水平衰减（t1/2 = 8秒），以接近基础浓度，然后上升到一个长期的平台期升高[Ca 2 +]i（如使用Quin 2测量）。紧随[Ca 2 +]i的这些变化之后，TRH刺激了催乳素和生长激素分泌速率明显但短暂的快速“尖峰期”，然后是长期增强的“平台期”。这两个阶段解离使用两类药物：离子载体离子霉素，和钙通道拮抗剂硝苯地平。离子霉素（100 nM）通过快速排空TRH调节的细胞内Ca 2+储库以在[Ca 2 +]i中产生TRH样峰，特异性阻断（小于90%）TRH作用的峰期;硝苯地平通过阻止电压依赖性Ca 2+通道的Ca 2+内流，抑制（小于50%）TRH诱导的[Ca 2 +]i和激素分泌变化的平台期。这些药物表明，促甲状腺激素释放激素诱导的尖峰在GH细胞中的[Ca 2 +]i是由释放离子霉素敏感池的细胞Ca 2+与一个小的组件（10%），由于细胞外Ca 2+的流入。TRH诱导的[Ca 2 +]i平台是由于细胞外Ca 2+的内流，其中约一半通过电压依赖性钙通道进入，另一半通过硝苯地平/维拉帕米不敏感的内流进入。TRH诱导的[Ca 2 +]i峰导致激素分泌的爆发，[Ca 2 +]i的平台期产生长时间的分泌增强; TRH独立产生峰期和平台期。[Ca ~（2+）]i的峰值是诱导激素爆发性释放所必需的，但不是充分的，而激素分泌速率的延长与稳态[Ca ~（2+）]i密切相关。
In clonal rat pituitary cells (GH cells), thyrotropin-releasing hormone (TRH) induced a pattern of changes in cytosolic free calcium concentrations [( Ca2+]i) composed of two phases: an acute spike phase to micromolar levels which decayed (t1/2 = 8 s) to a near-basal concentration and then rose to a prolonged plateau phase of elevated [Ca2+]i (as measured using Quin 2). Closely following these changes in [Ca2+]i, TRH stimulated a rapid “spike phase” of pronounced, but brief, enhancement of the rate of prolactin and growth-hormone secretion and then a “plateau phase” of prolonged enhancement. These two phases were dissociated using two classes of pharmacologic agents: the ionophore ionomycin, and a calcium channel antagonist nifedipine. Ionomycin (100 nM) specifically blocked (less than 90%) the spike phase of TRH action by rapidly emptying the TRH-regulated reservoir of cellular Ca2+ to generate a TRH-like spike in [Ca2+]i; nifedipine inhibited (less than 50%) the plateau phase of TRH-induced changes in [Ca2+]i and hormone secretion by preventing Ca2+ influx through voltage-dependent Ca2+ channels. These agents demonstrated that the TRH-induced spike in [Ca2+]i in GH cells is caused by release of an ionomycin-sensitive pool of cellular Ca2+ with a small component (10%) due to influx of extracellular Ca2+. The TRH-induced plateau in [Ca2+]i is due to influx of extracellular Ca2+, about half of which enters through voltage-dependent calcium channels and half of which enters via nifedipine/verapamil-insensitive influx. The TRH-induced spike in [Ca2+]i led to a burst in hormone secretion, and the plateau in [Ca2+]i produced a prolonged enhancement of secretion; the spike and plateau phases were generated independently by TRH. A spike in [Ca2+]i is necessary, but not sufficient, to induce burst release of hormone, while the prolonged rate of hormone secretion is intimately related to the steady-state [Ca2+]i.