INTRACELLULAR SIGNALING IN ENDOCRINE CELLS

电压敏感型和非敏感型钙离子通道的集成 促性腺激素释放激素(GnRH)诱导钙离子的途径 对黄体生成素(LH)的动员和释放进行了研究 垂体前叶促性腺激素细胞。通过以下途径增加钙进入 制霉菌素穿孔细胞中的电压敏感钙通道 对促性腺激素释放激素诱导的钙离子有两种不同的积极作用 放手。它有助于减少导致 增加尖峰的频率，也放大钙 通过增加钙的持续时间和幅度来传递信号 震荡。在细胞中观察到同样的效果，在细胞中 振荡由InsP3诱导。垂体促性腺激素细胞也表达 ATP门控受体通道。它们的激活会导致钙内流和 随之而来的是细胞内钙浓度的增加。嘌呤能 通道对电压不敏感，但它们的激活与 促性腺激素细胞的去极化和促性腺激素的附加易化 钙离子通过电压敏感的钙通道进入。嘌呤能 通道介导的钙内流也影响激动剂诱导的和 InsP3依赖的钙振荡通过增加频率， 基准线和尖峰持续时间。电压敏感型和电压型 ATP门控钙通道对钙尖峰频率的影响 与模拟钙离子尖峰的模型一致，其中一个小 细胞内钙浓度的增加能够引发大量的 在InsP3恒定存在下的钙振荡脉冲 集中精神。这两条钙内流途径也增强了促性腺激素释放激素诱导的 促黄体生成素释放。促性腺激素细胞与黄体生成素共同分泌三磷酸腺苷， 提示嘌呤能神经递质表达的生理意义 这些细胞中的通道。在周围的垂体细胞中，三磷酸腺苷迅速 被胞外-ATPase、胞外-ADPase和胞外-5‘核苷酸酶降解为 腺苷以钙/镁依赖的方式。这些观察结果 表示ATP在以下方面代表正反馈元素 激动剂诱导的钙信号和促性腺激素分泌，以及 这一作用是由胞外核苷酸酶控制的。

The integration of voltage-sensitive and -insensitive calcium entry pathways in gonadotropin-releasing hormone (GnRH)-induced calcium mobilization and luteinizing hormone (LH) release were investigated in anterior pituitary gonadotrophs. Increase in calcium entry through voltage-sensitive calcium channels in nystatin-perforated cells is associated with two distinct positive effects on GnRH-evoked calcium release. It facilitates a decrease in the interspike periods that lead to increase in the frequency of spiking and also magnifies calcium signaling by increasing the duration and amplitude of calcium oscillations. The same effects are observed in cells in which calcium oscillations are induced by InsP3. Pituitary gonadotrophs also express ATP-gated receptor channels. Their activation causes calcium influx and a consequent increase in cytosolic calcium concentrations. Purinergic channels are voltage-insensitive, but their activation is associated with the depolarization of gonadotrophs and the additional facilitation of calcium entry through voltage-sensitive calcium channels. Purinergic channel-mediated calcium influx also affects agonist-induced and InsP3-dependent calcium oscillations by increasing the frequency, baseline, and duration of spiking. The effects of voltage-sensitive and ATP-gated calcium channels on the frequency of calcium spiking are consistent with the model simulation of calcium spiking, in which a small increase in cytosolic calcium concentrations is able to trigger a large pulse of calcium oscillations in the presence of a constant InsP3 concentration. Both calcium entry pathways also potentiate GnRH-induced LH release. Gonadotrophs were found to co-secrete ATP with LH, indicating the physiological significance of the expression of purinergic channels in these cells. In perifused pituitary cells, ATP is promptly degraded by ecto-ATPase, ecto-ADPase, and ecto-5' nucleotidase to adenosine in a calcium/magnesium-dependent manner. These observations indicate that ATP represents a positive feedback element in agonist-induced calcium signaling and gonadotropin secretion, and that this action is controlled by ectonucleotidases.